Mental disorders of known aetiology and precision medicine in psychiatry: a promising but neglected alliance

PubMed Central

Fraguas, D.; Díaz-Caneja, C. M.; State, M. W.; O’Donovan, M. C.; Gur, R. E.; Arango, C.

2016-01-01

Personalized or precision medicine is predicated on the assumption that the average response to treatment is not necessarily representative of the response of each individual. A commitment to personalized medicine demands an effort to bring evidence-based medicine and personalized medicine closer together. The use of relatively homogeneous groups, defined using a priori criteria, may constitute a promising initial step for developing more accurate risk-prediction models with which to advance the development of personalized evidence-based medicine approaches to heterogeneous syndromes such as schizophrenia. However, this can lead to a paradoxical situation in the field of psychiatry. Since there has been a tendency to loosely define psychiatric disorders as ones without a known aetiology, the discovery of an aetiology for psychiatric syndromes (e.g. 22q11.2 deletion syndrome in some cases of schizophrenia), while offering a path toward more precise treatments, may also lead to their reclassification away from psychiatry. We contend that psychiatric disorders with a known aetiology should not be removed from the field of psychiatry. This knowledge should be used instead to guide treatment, inasmuch as psychotherapies, pharmacotherapies and other treatments can all be valid approaches to mental disorders. The translation of the personalized clinical approach inherent to psychiatry into evidence-based precision medicine can lead to the development of novel treatment options for mental disorders and improve outcomes. PMID:27334937

Craniofacial and dental malformations in Costello syndrome: A detailed evaluation using multi-detector row computed tomography.

PubMed

Takahashi, Masashi; Ohashi, Hirofumi

2013-06-01

Costello syndrome is a rare multiple congenital anomaly syndrome caused by heterozygous germline HRAS mutations, which is characterized by intellectual disability, growth retardation, distinctive facies, loose skin, cardiomyopathy and a preposition to malignancies. Although teeth abnormalities have been encountered in nearly two-thirds of the patients in literature, the evaluation tended to be limited to the extent which can be obtained from physical examination. We investigated detailed craniofacial, oral and dental findings in four patients with Costello syndrome. In this study, images reconstructed by multi-detector row computed tomography (MDCT) were used as substitutes for dental cast study and panoramic and lateral cephalometric radiograph studies to evaluate dental arches, tooth size, relationships between craniofacial and dental structures, and hypodontia. All four patients showed true/relative macrocephaly with facial bone hypoplasia and gingival hypertrophy. Occlusal attrition, malocclusion, small dental arches, microdontia, and convex face were noted in three patients. In addition, one patient showed dental caries, conic tooth and gingivitis, and another patient showed hypodontia. Our study suggests that craniofacial and dental abnormalities are common in Costello syndrome patients and comprehensive dental care should be provided from early infancy. To our knowledge, this is the first study of thorough craniofacial and dental evaluation by using MDCT in Costello syndrome. MDCT is a useful tool for precise evaluation of craniofacial and oral manifestations in patients with congenital anomaly/intellectual disability syndromes. © 2012 The Authors. Congenital Anomalies © 2012 Japanese Teratology Society.

Nosology and Diagnosis of Rett Syndrome

ERIC Educational Resources Information Center

Matson, Johnny L.; Fodstad, Jill C.; Boisjoli, Jessica A.

2008-01-01

Rett Syndrome is one of the least commonly occurring autism spectrum disorders (ASD), but certainly one of the most devastating. A genetic profile has been identified, but checklists still have an important role for prescreening, especially before expensive genetic testing, and to provide precise strengths and weaknesses with respect to the core…

Concepts, Diagnosis and the History of Medicine: Historicising Ian Hacking and Munchausen Syndrome

PubMed Central

Millard, Chris

2017-01-01

Summary Concepts used by historians are as historical as the diagnoses or categories that are studied. The example of Munchausen syndrome (deceptive presentation of illness in order to adopt the ‘sick role’) is used to explore this. Like most psychiatric diagnoses, Munchausen syndrome is not thought applicable across time by social historians of medicine. It is historically specific, drawing upon twentieth-century anthropology and sociology to explain motivation through desire for the ‘sick role’. Ian Hacking’s concepts of ‘making up people’ and ‘looping effects’ are regularly utilised outside of the context in which they are formed. However, this context is precisely the same anthropological and sociological insight used to explain Munchausen syndrome. It remains correct to resist the projection of Munchausen syndrome into the past. However, it seems inconsistent to use Hacking’s concepts to describe identity formation before the twentieth century as they are given meaning by an identical context. PMID:29713120

Seckel's syndrome and malformations of cortical development: report of three new cases and review of the literature.

PubMed

Capovilla, G; Lorenzetti, M E; Montagnini, A; Borgatti, R; Piccinelli, P; Giordano, L; Accorsi, P; Caudana, R

2001-05-01

Seckel's syndrome is a rare form of primordial dwarfism, characterized by peculiar facial appearance. In the past, this condition was overdiagnosed, and most attention was given to the facial and skeletal features to define more precise diagnostic criteria. The presence of mental retardation and neurologic signs is one of the peculiar features of this syndrome, but only recently were rare cases of malformation of cortical development described, as documented by magnetic resonance imaging (MRI). Here, we present three new cases of Seckel's syndrome showing different malformations of cortical development (one gyral hypoplasia, one macrogyria and partial corpus callosum agenesis, and one bilateral opercular macrogyria). We hypothesize that the different types of clinical expression of our patients could be explained by different malformation of cortical development types. We think that MRI studies could be performed in malformative syndromes because of the possible correlations between type and extent of the lesion and the clinical picture of any individual case.

Early Vocal Development in Autism Spectrum Disorder, Rett Syndrome, and Fragile X Syndrome: Insights from Studies using Retrospective Video Analysis.

PubMed

Roche, Laura; Zhang, Dajie; Bartl-Pokorny, Katrin D; Pokorny, Florian B; Schuller, Björn W; Esposito, Gianluca; Bölte, Sven; Roeyers, Herbert; Poustka, Luise; Gugatschka, Markus; Waddington, Hannah; Vollmann, Ralf; Einspieler, Christa; Marschik, Peter B

2018-03-01

This article provides an overview of studies assessing the early vocalisations of children with autism spectrum disorder (ASD), Rett syndrome (RTT), and fragile X syndrome (FXS) using retrospective video analysis (RVA) during the first two years of life. Electronic databases were systematically searched and a total of 23 studies were selected. These studies were then categorised according to whether children were later diagnosed with ASD (13 studies), RTT (8 studies), or FXS (2 studies), and then described in terms of (a) participant characteristics, (b) control group characteristics, (c) video footage, (d) behaviours analysed, and (e) main findings. This overview supports the use of RVA in analysing the early development of vocalisations in children later diagnosed with ASD, RTT or FXS, and provides an in-depth analysis of vocalisation presentation, complex vocalisation production, and the rate and/or frequency of vocalisation production across the three disorders. Implications are discussed in terms of extending crude vocal analyses to more precise methods that might provide more powerful means by which to discriminate between disorders during early development. A greater understanding of the early manifestation of these disorders may then lead to improvements in earlier detection.

The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes

PubMed Central

Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P.; Panayiotidis, Panayiotis

2015-01-01

Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. PMID:26190429

Idiopathic ophthalmodynia and idiopathic rhinalgia: two topographic facial pain syndromes.

PubMed

Pareja, Juan A; Cuadrado, María L; Porta-Etessam, Jesús; Fernández-de-las-Peñas, César; Gili, Pablo; Caminero, Ana B; Cebrián, José L

2010-09-01

To describe 2 topographic facial pain conditions with the pain clearly localized in the eye (idiopathic ophthalmodynia) or in the nose (idiopathic rhinalgia), and to propose their distinction from persistent idiopathic facial pain. Persistent idiopathic facial pain, burning mouth syndrome, atypical odontalgia, and facial arthromyalgia are idiopathic facial pain syndromes that have been separated according to topographical criteria. Still, some other facial pain syndromes might have been veiled under the broad term of persistent idiopathic facial pain. Through a 10-year period we have studied all patients referred to our neurological clinic because of facial pain of unknown etiology that might deviate from all well-characterized facial pain syndromes. In a group of patients we have identified 2 consistent clinical pictures with pain precisely located either in the eye (n=11) or in the nose (n=7). Clinical features resembled those of other localized idiopathic facial syndromes, the key differences relying on the topographic distribution of the pain. Both idiopathic ophthalmodynia and idiopathic rhinalgia seem specific pain syndromes with a distinctive location, and may deserve a nosologic status just as other focal pain syndromes of the face. Whether all such focal syndromes are topographic variants of persistent idiopathic facial pain or independent disorders remains a controversial issue.

Effect of Raw Crushed Garlic (Allium sativum L.) on Components of Metabolic Syndrome.

PubMed

Choudhary, Prema Ram; Jani, Rameshchandra D; Sharma, Megh Shyam

2017-09-28

Metabolic syndrome consists of a group of risk factors characterized by abdominal obesity, hypertension, atherogenic dyslipidemia, hyperglycemia, and prothrombotic and proinflammatory conditions. Raw garlic homogenate has been reported to reduce serum lipid levels in animal model; however, no precise studies have been performed to evaluate the effect of raw crushed garlic (Allium sativum L.) on components of metabolic syndrome. Therefore, the present study was designed to investigate the effect of raw crushed garlic on components of metabolic syndrome. A total of 40 metabolic syndrome patients were randomly selected from the diabetic center of SP Medical College, Bikaner, Rajasthan, India. They underwent treatment with 100 mg/kg body weight raw crushed garlic 2 times a day with standard diet for 4 weeks; their anthropometric and serum biochemical variables were measured at both the beginning and the end of the study. Statistical analysis was performed using IBM SPSS version 20, and Student's paired "t" test was used to compare variables before and after treatment with garlic preparation. Raw crushed garlic significantly reduced components of metabolic syndrome including waist circumference (p < .05), systolic and diastolic blood pressure (p < .001), triglycerides (p < .01), fasting blood glucose (p < .0001) and significantly increased serum high-density lipoprotein cholesterol (p < .0001). There was no significant difference found in body mass index (p > .05) of patients with metabolic syndrome after consumption of raw crushed garlic for 4 weeks. Raw crushed garlic has beneficial effects on components of metabolic syndrome; therefore, it can be used as an accompanying remedy for prevention and treatment of patients with metabolic syndrome.

Usher syndrome: an effective sequencing approach to establish a genetic and clinical diagnosis.

PubMed

Lenarduzzi, S; Vozzi, D; Morgan, A; Rubinato, E; D'Eustacchio, A; Osland, T M; Rossi, C; Graziano, C; Castorina, P; Ambrosetti, U; Morgutti, M; Girotto, G

2015-02-01

Usher syndrome is an autosomal recessive disorder characterized by retinitis pigmentosa, sensorineural hearing loss and, in some cases, vestibular dysfunction. The disorder is clinically and genetically heterogeneous and, to date, mutations in 11 genes have been described. This finding makes difficult to get a precise molecular diagnosis and offer patients accurate genetic counselling. To overcome this problem and to increase our knowledge of the molecular basis of Usher syndrome, we designed a targeted resequencing custom panel. In a first validation step a series of 16 Italian patients with known molecular diagnosis were analysed and 31 out of 32 alleles were detected (97% of accuracy). After this step, 31 patients without a molecular diagnosis were enrolled in the study. Three out of them with an uncertain Usher diagnosis were excluded. One causative allele was detected in 24 out 28 patients (86%) while the presence of both causative alleles characterized 19 patients out 28 (68%). Sixteen novel and 27 known alleles were found in the following genes: USH2A (50%), MYO7A (7%), CDH23 (11%), PCDH15 (7%) and USH1G (2%). Overall, on the 44 patients the protocol was able to characterize 74 alleles out of 88 (84%). These results suggest that our panel is an effective approach for the genetic diagnosis of Usher syndrome leading to: 1) an accurate molecular diagnosis, 2) better genetic counselling, 3) more precise molecular epidemiology data fundamental for future interventional plans. Copyright © 2014 Elsevier B.V. All rights reserved.

Pain perception in people with Down syndrome: a synthesis of clinical and experimental research

PubMed Central

McGuire, Brian E.; Defrin, Ruth

2015-01-01

People with an intellectual disability experience both acute and chronic pain with at least the same frequency as the general population. However, considerably less is known about the pain perception of people with Down syndrome. In this review paper, we evaluated the available clinical and experimental evidence. Some experimental studies of acute pain have indicated that pain threshold was higher than normal but only when using a reaction time method to measure pain sensitivity. However, when reaction time is not part of the calculation of the pain threshold, pain sensitivity in people with Down syndrome is in fact lower than normal (more sensitive to pain). Clinical studies of chronic pain have shown that people with an intellectual disability experience chronic pain and within that population, people with Down syndrome also experience chronic pain, but the precise prevalence of chronic pain in Down syndrome has yet to be established. Taken together, the literature suggests that people with Down syndrome experience pain, both acute and chronic, with at least the same frequency as the rest of the population. Furthermore, the evidence suggests that although acute pain expression appears to be delayed, once pain is registered, there appears to be a magnified pain response. We conclude by proposing an agenda for future research in this area. PMID:26283936

Survey of recognition and treatment of at-risk mental state by Japanese psychiatrists.

PubMed

Tsujino, Naohisa; Tagata, Hiromi; Baba, Yoko; Kojima, Akiko; Yamaguchi, Taiju; Katagiri, Naoyuki; Nemoto, Takahiro; Mizuno, Masafumi

2018-02-27

The importance of early intervention in psychiatry is widely recognized among psychiatrists. However, it is unknown whether precise knowledge of at-risk mental state has been disseminated. With this survey, we aimed to reveal how Japanese psychiatrists diagnose patients with at-risk mental state and prescribe treatment strategies for them. Using fictional case vignettes, we conducted a questionnaire survey of psychiatrists (n = 1399) who worked in Tokyo. We mailed study documents to all eligible participants in November 2015 with a requested return date in December. Two hundred and sixty (19.3%) psychiatrists responded to the survey. Their correct diagnosis rates for the patients in the at-risk mental state vignettes were low (14.6% for the vignette describing at-risk mental state with attenuated positive symptom syndrome; 13.1% for the vignette describing at-risk mental state with brief intermittent psychotic syndrome). Many psychiatrists selected pharmacotherapy and antipsychotics to treat patients in the at-risk mental state vignettes. The psychiatrists who correctly diagnosed patients in the at-risk mental state vignettes had significantly fewer years of clinical psychiatric experience than did those who diagnosed them as having a non-at-risk mental state (12.5 years vs 22.7 years for the vignette describing at-risk mental state with attenuated positive symptom syndrome, P < 0.01; 14.3 years vs 22.2 years for the vignette describing at-risk mental state with brief intermittent psychotic syndrome, P < 0.01). This study suggests that precise knowledge of at-risk mental state has not been disseminated among Japanese psychiatrists. © 2018 The Authors. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology.

Benign Childhood Focal Epilepsies: Assessment of Established and Newly Recognized Syndromes

ERIC Educational Resources Information Center

Panayiotopoulos, Chrysostomos P.; Michael, Michael; Sanders, Sue; Valeta, Thalia; Koutroumanidis, Michael

2008-01-01

A big advance in epileptology has been the recognition of syndromes with distinct aetiology, clinical and EEG features, treatment and prognosis. A prime and common example of this is rolandic epilepsy that is well known by the general paediatricians for over 50 years, thus allowing a precise diagnosis that predicts an excellent prognosis. However,…

Takotsubo cardiomyopathy associated with cardiac arrest following cardiac surgery: new variants of an unusual syndrome.

PubMed

Vernick, William J; Hargrove, W Clark; Augoustides, John G; Horak, Jiri

2010-11-01

Takotsubo cardiomyopathy is increasingly being recognized in the perioperative period. To date, there have been only three previous cases involving cardiac surgery reported and this represents the fourth case. The precise mechanism remains elusive, and there is no definitive management strategy. It appears that the syndromes course in cardiac surgical patients is self-limited. This syndrome must now be considered in the differential diagnosis of postcardiotomy cardiac failure. © 2010 Wiley Periodicals, Inc.

Next generation phenotyping using narrative reports in a rare disease clinical data warehouse.

PubMed

Garcelon, Nicolas; Neuraz, Antoine; Salomon, Rémi; Bahi-Buisson, Nadia; Amiel, Jeanne; Picard, Capucine; Mahlaoui, Nizar; Benoit, Vincent; Burgun, Anita; Rance, Bastien

2018-05-31

Secondary use of data collected in Electronic Health Records opens perspectives for increasing our knowledge of rare diseases. The clinical data warehouse (named Dr. Warehouse) at the Necker-Enfants Malades Children's Hospital contains data collected during normal care for thousands of patients. Dr. Warehouse is oriented toward the exploration of clinical narratives. In this study, we present our method to find phenotypes associated with diseases of interest. We leveraged the frequency and TF-IDF to explore the association between clinical phenotypes and rare diseases. We applied our method in six use cases: phenotypes associated with the Rett, Lowe, Silver Russell, Bardet-Biedl syndromes, DOCK8 deficiency and Activated PI3-kinase Delta Syndrome (APDS). We asked domain experts to evaluate the relevance of the top-50 (for frequency and TF-IDF) phenotypes identified by Dr. Warehouse and computed the average precision and mean average precision. Experts concluded that between 16 and 39 phenotypes could be considered as relevant in the top-50 phenotypes ranked by descending frequency discovered by Dr. Warehouse (resp. between 11 and 41 for TF-IDF). Average precision ranges from 0.55 to 0.91 for frequency and 0.52 to 0.95 for TF-IDF. Mean average precision was 0.79. Our study suggests that phenotypes identified in clinical narratives stored in Electronic Health Record can provide rare disease specialists with candidate phenotypes that can be used in addition to the literature. Clinical Data Warehouses can be used to perform Next Generation Phenotyping, especially in the context of rare diseases. We have developed a method to detect phenotypes associated with a group of patients using medical concepts extracted from free-text clinical narratives.

Paroxysmal supraventricular tachycardia and Wolff-Parkinson-White syndrome in ankylosing spondylitis: a large cohort observation study and literature review.

PubMed

Ho, Huei-Huang; Yeh, San-Jou; Tsai, Wen-Pin; Wang, Chin-Man; Chen, Ji Yih

2012-12-01

To investigate the associations of paroxysmal supraventricular tachycardia (PSVT) and Wolff-Parkinson-White (WPW) syndrome with ankylosing spondylitis (AS). We conducted a retrospective cohort study by reviewing the medical records of 1503 consecutive AS patients diagnosed at a tertiary medical center. The clinical and electrocardiographic (ECG) characteristics of 641 AS patients having 12-lead ECG available were further analyzed in a precise manner. Among the 641 AS patients with 12-lead ECG available for detecting cardiac abnormalities, 14 were identified as having PSVT, including 3 with WPW syndrome and 1 having a WPW (ventricular preexcitation) ECG pattern. A higher proportion of AS patients presented with PSVT (21.8/1000) compared with a general population-based study (2.25/1000). Also, AS patients demonstrated a higher prevalence of WPW syndrome or WPW pattern (6.24/1000) than found in general population-based studies (0.9 to 1.5/1000). Ankylosing spondylitis patients with PSVT or WPW syndrome had significantly higher rates of peripheral arthritis (78.6%; P = 0.002), acute anterior uveitis (64.3%; P = 0.003), bamboo spine (64.3%; P = 0.001), and other cardiovascular disorders (85.7%; P < 0.0001) than the remaining 627 patients without PSVT. Ankylosing spondylitis patients had a high probability of developing PSVT and WPW syndrome. Detailed ECG and electrophysiological examinations are required for early detection of PSVT and WPW syndrome for prompt resolution of potentially life-threatening complications in all AS patients, especially those presenting with the symptoms of palpitation, dizziness, dyspnea, or syncope. Copyright © 2012 Elsevier Inc. All rights reserved.

Specific Features of Dumping Syndrome after Various Types of Gastrectomy as Assessed by a Newly Developed Integrated Questionnaire, the PGSAS-45.

PubMed

Tanizawa, Yutaka; Tanabe, Kazuaki; Kawahira, Hiroshi; Fujita, Junya; Takiguchi, Nobuhiro; Takahashi, Masazumi; Ito, Yuichi; Mitsumori, Norio; Namikawa, Tsutomu; Oshio, Atsushi; Nakada, Koji

2016-01-01

Dumping syndrome is a well-known adverse outcome after gastrectomy, but the precise clinical features have not been described. The aim of this study was to examine global aspects of dumping syndrome and to explore factors affecting the intensity of dumping syndrome in a large cohort using a newly developed integrated questionnaire, the Post-Gastrectomy Syndrome Assessment Scale (PGSAS)-45. Eligible questionnaires retrieved from 2,368 patients after 6 types of gastrectomy were analyzed. The incidence, intensity and number of symptoms of early general, early abdominal and late dumping syndrome were examined across various types of gastrectomy, and clinical factors affecting the intensity of each category of dumping syndrome were identified by multiple regression analysis. Dumping syndromes occurred most frequently and strongly in patients who underwent total gastrectomy with Roux-en-Y (TGRY), followed by proximal gastrectomy (PG), distal gastrectomy with Billroth-I, distal gastrectomy with Roux-en-Y, pylorus-preserving gastrectomy (PPG) and local resection (LR), in that order. Significant positive correlations among different categories of dumping syndromes were observed. TGRY, female sex, younger age, division of the celiac branch of the vagus nerve, PG and shorter postoperative period were independently related to worse dumping syndrome. Dumping syndromes were most common after TGRY and least common after PPG and LR among the various gastrectomy procedures. Type of gastrectomy and several clinical factors were related to the intensity of dumping syndrome. PGSAS-45 could offer a useful tool for evaluating dumping syndrome after gastrectomy. © 2015 S. Karger AG, Basel.

Wall paintings facies and their possible genetic correlates in the ancient Pompeii: A bio-anthropologic message from the past?

PubMed

Ponti, Giovanni; Manfredini, Marco; Ruini, Cristel

2016-09-10

The figurative arts and precisely the ancient Pompeian wall paintings portraits can provide an additional source of information in supplementing bio-anthropological studies. There are several genetic diseases with a wide spectrum of congenital bone stigmata in association to distinctive facial features. Gorlin-Goltz syndrome, also named nevoid basal cell carcinoma syndrome, is an autosomal dominant syndrome characterized by unusual skeletal changes, such as macrocephaly, facial asymmetry, hypertelorism, frontal and parietal bossing caused by germline mutations of the gene PTCH1. The Gorlin syndrome, clinically defined in 1963, existed during Dynastic Egyptian times, as revealed by a spectrum of skeletal findings compatible with the syndrome in mummies dating back to three thousand years ago and, most likely, in the ancient population of Pompeii. In the present research, we discuss the potential relationship between Pompeian wall paintings portrait and the cranio-metric bone changes revealed among the Pompeian skull collections assuming that the ancient portraits can constitute an important tool that should be strictly integrated with osteologic and biomolecular data in order to argue a syndromic diagnosis in ancient population. Copyright © 2016 Elsevier B.V. All rights reserved.

[Münchausen syndrome by proxy].

PubMed

Berent, Dominika; Florkowski, Antoni; Gałecki, Piotr

2010-01-01

Münchausen syndrome by proxy (MSBP), is a psychiatric disorder, a particular form of child abuse. An impaired emotional relationship exists mainly between the mother and her child. According to the variety of victims' symptoms, all medicine doctors may deal with this syndrome in every day clinical practice. Still insufficient knowledge about the syndrome and its' rare consideration in the differential diagnosis result in only severe, potentially lethal cases recognition. For many years the rest remains a source of a long-term physical and mental injuries in victims. About 30 years from the first attempt to precisely point the signalling symptoms for a proper diagnosis, we present the current knowledge on epidemiology, aetiology, diagnostic criteria, advised management and psychological portrait of the mother with the syndrome and her child, the syndrome's victim.

Feasibility of a Novel Functional Sensibility Test as an Assisted Examination for Determining Precision Pinch Performance in Patients with Carpal Tunnel Syndrome

PubMed Central

Hsu, Hsiu-Yun; Kuo, Li-Chieh; Kuo, Yao-Lung; Chiu, Haw-Yen; Jou, I-Ming; Wu, Po-Ting; Su, Fong-Chin

2013-01-01

To understand the feasibility of a novel functional sensibility test for determining precision pinch performance in patients with carpal tunnel syndrome, this study investigates the validity, sensitivity and specificity of functional sensibility derived from a pinch-holding-up activity (PHUA) test. Participants include 70 clinically defined carpal tunnel syndrome (CTS) patients with 119 involved hands and 70 age- and gender-matched controls. To examine the discriminating ability of the functional sensibility test, the differences in the ability of pinch force adjustments to the inertial load of handling object between CTS and control subjects are analyzed. The results of functional sensibility are correlated with the severity of CTS to establish concurrent validity. The receiver operating characteristic (ROC) curve is constructed to demonstrate the accuracy of the proposed test. The functional sensibility score significantly discriminates the patients and control groups (respectively, 12.94±1.72 vs. 11.51±1.15N in peak pinch force (FPPeak), p<0.001; 2.92±0.41 vs. 2.52±0.24 in force ratio, p<0.001) and is moderately correlated (r = 0.42–0.54, p<0.001) with the results of traditional sensibility tests (touch-pressure threshold and two-point discrimination test). In addition, there is a statistical difference in the results of functional sensibility (p<0.001) among the subgroups of CTS severity based on electrophysiological study. The sensitivity and specificity are 0.79 and 0.76, respectively, for the functional sensibility test. The areas under the ROC curve are 0.85 and 0.80 for the force ratio and FPPeak, respectively. In conclusion, the functional sensibility test could be feasibly used as a clinical tool for determining both the sensibility and precision pinch performance of hands for the patients with CTS. PMID:23977209

Comparison of the efficacy of three PubMed search filters in finding randomized controlled trials to answer clinical questions.

PubMed

Yousefi-Nooraie, Reza; Irani, Shirin; Mortaz-Hedjri, Soroush; Shakiba, Behnam

2013-10-01

The aim of this study was to compare the performance of three search methods in the retrieval of relevant clinical trials from PubMed to answer specific clinical questions. Included studies of a sample of 100 Cochrane reviews which recorded in PubMed were considered as the reference standard. The search queries were formulated based on the systematic review titles. Precision, recall and number of retrieved records for limiting the results to clinical trial publication type, and using sensitive and specific clinical queries filters were compared. The number of keywords, presence of specific names of intervention and syndrome in the search keywords were used in a model to predict the recalls and precisions. The Clinical queries-sensitive search strategy retrieved the largest number of records (33) and had the highest recall (41.6%) and lowest precision (4.8%). The presence of specific intervention name was the only significant predictor of all recalls and precisions (P = 0.016). The recall and precision of combination of simple clinical search queries and methodological search filters to find clinical trials in various subjects were considerably low. The limit field strategy yielded in higher precision and fewer retrieved records and approximately similar recall, compared with the clinical queries-sensitive strategy. Presence of specific intervention name in the search keywords increased both recall and precision. © 2010 John Wiley & Sons Ltd.

Retrospective diagnosis of Kindler syndrome in a 37-year-old man.

PubMed

Thomson, M A; Ashton, G H S; McGrath, J A; Eady, R A J; Moss, C

2006-01-01

Kindler syndrome is a rare autosomal recessive disorder characterized by acral blisters in infancy and early childhood, followed by photosensitivity, progressive poikiloderma and cutaneous atrophy. Other features include webbing of the toes and fingers, palmoplantar hyperkeratosis, gingival fragility, poor dentition, and mucosal involvement in the form of urethral, anal and oesophageal stenosis. The recent finding of KIND1 mutations in Kindler syndrome facilitates early diagnosis, prophylactic measures and more precise definition of the phenotype. In the family described here, molecular diagnosis of Kindler syndrome in an infant with acral blisters led to the belated diagnosis in a severely affected relative whose condition had remained unidentified for 37 years.

Role of Autophagy in Metabolic Syndrome-Associated Heart Disease

PubMed Central

Ren, Sidney Y.; Xu, Xihui

2014-01-01

Metabolic syndrome (MetS) is a constellation of multiple metabolic risk factors including abdominal obesity, glucose intolerance, insulin resistance, dyslipidemia and hypertension. Over the past decades, the prevalence of metabolic syndrome has increased dramatically, imposing a devastating, pandemic health threat. More importantly, individuals with metabolic syndrome are at an increased risk of diabetes mellitus and overall cardiovascular diseases. One of the common comorbidities of metabolic syndrome is heart anomalies leading to the loss of cardiomyocytes, cardiac dysfunction and ultimately heart failure. Up-to-date, a plethora cell signaling pathways have been postulated for the pathogenesis of cardiac complications in obesity including lipotoxicity, inflammation, oxidative stress, apoptosis and sympathetic overactivation although the precise mechanism of action underscoring obesity-associated heart dysfunction remains elusive. Recent evidence has indicated a potential role of protein quality control in components of metabolic syndrome. Within the protein quality control system, the autophagy-lysosome pathway is an evolutionarily conserved pathway responsible for bulk degradation of large intracellular organelles and protein aggregates. Autophagy has been demonstrated to play an indispensible role in the maintenance of cardiac geometry and function under both physiological and pathological conditions. Accumulating studies have demonstrated that autophagy plays a pivotal role in the etiology of cardiac anomalies under obesity and metabolic syndrome. In this mini review, we will discuss on how autophagy is involved in the regulation of cardiac function in obesity and metabolic syndrome. PMID:24810277

Metabolic Syndrome and Risk of Development of Atrial Fibrillation

PubMed Central

Watanabe, Hiroshi; Tanabe, Naohito; Watanabe, Toru; Darbar, Dawood; Roden, Dan M.; Sasaki, Shigeru; Aizawa, Yoshifusa

2008-01-01

Background The metabolic syndrome consists of a cluster of atherosclerotic risk factors, many of which also have been implicated in the genesis of atrial fibrillation (AF). However, the precise role of the metabolic syndrome in the development of AF is unknown. Methods and Results This prospective, community-based, observational cohort study was based on an annual health check-up program in Japan. We studied 28 449 participants without baseline AF. We used 2 different criteria for the metabolic syndrome—the guidelines of the National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III) and those of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI)—to study the risk of development of new-onset AF. The metabolic syndrome was present in 3716 subjects (13%) and 4544 subjects (16%) using the NCEP-ATP III and AHA/NHLBI definitions, respectively. During a mean follow-up of 4.5 years, AF developed in 265 subjects (105 women). Among the metabolic syndrome components, obesity (age- and sex-adjusted hazard ratio [HR], 1.64), elevated blood pressure (HR, 1.69), low high-density lipoprotein cholesterol (HR, 1.52), and impaired insulin tolerance (HR, 1.44 [NCEP-ATP III] and 1.35 [AHA/NHLBI]) showed an increased risk for AF. The association between the metabolic syndrome and AF remained significant in subjects without treated hypertension or diabetes by the NCEP-ATP III definition (HR, 1.78) but not by the AHA/NHLBI definition (HR, 1.28). Conclusions The metabolic syndrome was associated with increased risk of AF. The metabolic derangements of the syndrome may be important in the pathogenesis of AF. PMID:18285562

Phase analysis in the Wolff-Parkinson-White syndrome with surgically proven accessory conduction pathways: concise communication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakajima, K.; Bunko, H.; Tada, A.

1984-01-01

Twenty-one patients with the Wolff-Parkinson-White (WPW) syndrome who underwent surgical division of the accessory conduction pathway (ACP) were studied by gated blood-pool scintigraphy. In each case, a functional image of the phase was generated, based on the fundamental frequency of the Fourier transform. The location of the ACP was confirmed by electrophysiologic study, epicardial mapping, and surgery. Phase analysis identified the side of preexcitation correctly in 16 out of 20 patients with WPW syndrome with a delta wave. All patients with right-cardiac type (N=9) had initial contraction in the right ventricle (RV). In patients with left-cardiac type (N=10), six hadmore » initial movement in the left ventricle (LV); but in the other four the ACPs in the anterior or lateral wall of the left ventricle (LV) could not be detected. In patients with multiple ACPs (N=2), one right-cardiac type had initial contraction in the RV, while in the other (with an intermittent WPW syndrome) the ACP was not detected. These observations indicate that abnormal wall motion is associated with the conduction anomalies of the WPW syndrome. We conclude that phase analysis can correctly identify the side of initial contraction in the WPW syndrome before and after surgery. However, as a method of preoperative study, it seems difficult to determine the precise site of the ACP by phase analysis alone.« less

The association between blood lipid and phlegm turbidity syndrome of angina pectoris: a systematic review and meta-analysis.

PubMed

Kong, Dezhao; Wang, Yang; Liu, Yue; Zhang, Zhe; Liu, Guanghui; Qi, Wencheng; Xiao, Lei; Yuan, Dongchao; Yang, Guanlin

2014-08-01

A series of case-control studies have been conducted to investigate the association between blood lipid and phlegm turbidity syndrome of angina pectoris, but produced inconsistent results. We performed a meta-analysis to determine the association between blood lipid and phlegm turbidity syndrome of angina pectoris more precisely. Manual screening as well as screening of the China National Knowledge Infrastructure (CNKI), Chinese Journal full-text database (VIP), Wanfang database (WF), ScienceDirect, Pubmed, the Cochrane Library, and Embase were carried out for relevant literature. The formula was translated to calculate the pooled mean value and standard deviation value. The "Newcastle-Ottawa Quality Assessment Scale: Case-Control Studies" (NOS) was taken to assess the quality of the included studies. The Revman 5.2.6 software provided by "The Cochrane Collaboration" was used to analyze the collected data. The subgroup analysis was established according to the sample size proportion between the test group and the control group. Sensitivity analysis was constructed by using two different effect models. Besides, a funnel plot was created to analyze potential publication bias. No statistically meaningful difference existed between the test group and control group of total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) in non-Qi and yin deficiency syndrome (QYDS) and non-Yang deficiency syndrome (YDS) subgroup, whereas the two biotic indicators in the test group were higher than the non-phlegm syndrome group in other subgroups. Triglyceride (TG) in phlegm syndrome group showed superior to non-phlegm syndrome group in the rest subgroups except for the non-CCS (Cold coagulating syndrome)-non-YDS subgroup. High-density lipoprotein-cholesterol (HDL-C) levels of the phlegm group were lower than that of the non-phlegm group in all subgroups. When comparing with Traditional Chinese Medicine (TCM) syndromes of asthenia nature, such as YDS, QYDS, and heart qi deficiency syndrome), the levels of TG, TC, and LDL-C were higher in phlegm turbidity syndrome. However, for sthenia syndromes such as Qi stagnation syndrome (QSS), heart blood stasis syndrome (HBSS), and CCS, there was no obvious difference. Furthermore, HDL-C levels in the phlegm turbidity group were lower than those of the non-phlegm group. Nevertheless, these results should be confirmed with further studies. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vascular endothelial function and oxidative stress mechanisms in patients with Behçet's syndrome.

PubMed

Chambers, J C; Haskard, D O; Kooner, J S

2001-02-01

We sought to test the hypothesis that vascular endothelial function is impaired in Behçet's syndrome and reflects increased levels of oxidative stress. Behçet's syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Behçet's syndrome are not known. We studied 19 patients with Behçet's syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG)-induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. Flow-mediated dilation was reduced in patients with Behcet's syndrome as compared with control subjects (0.7 +/- 0.9% vs. 5.7 +/- 0.9%, p = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 +/- 0.2 vs. 4.0 +/- 0.2 mm, p = 0.47) or NTG-induced dilation (19.7 +/- 1.9% vs. 19.7 +/- 1.2%, p = 0.98). In regression analysis, Behçet's syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Behçet's syndrome (0.2 +/- 0.7% to 3.5 +/- 1.0%, p = 0.002), but not in control subjects (4.3 +/- 0.6% to 4.7 +/- 0.4%, p = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. Vascular endothelial function is impaired in Behcet's syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Behçet's syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder.

Diagnosis‐based emergency department alcohol harm surveillance: What can it tell us about acute alcohol harms at the population level?

PubMed Central

Dinh, Michael; Rodgers, Craig; Muscatello, David J.; McGuire, Rhydwyn; Ryan, Therese; Thackway, Sarah

2016-01-01

Abstract Introduction and Aims Acute harm from heavy drinking episodes is an increasing focus of public health policy, but capturing timely data on acute harms in the population is challenging. This study aimed to evaluate the precision of readily available administrative emergency department (ED) data in public health surveillance of acute alcohol harms. Design and Methods We selected a random sample of 1000 ED presentations assigned an ED diagnosis code for alcohol harms (the ‘alcohol syndrome’) in the New South Wales, Australia, automatic syndromic surveillance system. The sample was selected from 68 public hospitals during 2014. Nursing triage free‐text fields were independently reviewed to confirm alcohol consumption and classify each presentation into either an ‘acute’ or ‘chronic’ harm. Positive predictive value (PPV) for acute harm was calculated, and predictors of acute harm presentations were estimated using logistic regression. Results The PPV of the alcohol syndrome for acute alcohol harm was 53.5%. Independent predictors of acute harm were ambulance arrival [adjusted odds ratio (aOR) = 3.4, 95% confidence interval (CI) 2.4–4.7], younger age (12–24 vs. 25–39 years: aOR = 3.4, 95% CI 2.2–5.3), not being admitted (aOR 2.2, 95% CI 1.5–3.2) and arriving between 10 pm and 5.59 am (aOR 2.1, 95% CI 1.5–2.8). PPV among 12 to 24‐year‐olds was 82%. Discussion and Conclusions The alcohol syndrome provides moderate precision as an indicator of acute alcohol harms presenting to the ED. Precision for monitoring acute harm in the population is improved by filtering the syndrome by the strongest independent predictors of acute alcohol harm presentations. [Whitlam G, Dinh M, Rodgers C, Muscatello DJ, McGuire R, Ryan T, Thackway S. Diagnosis‐based emergency department alcohol harm surveillance: What can it tell us about acute alcohol harms at the population level? Drug Alcohol Rev 2016;35:693–701] PMID:27786390

Cornelia de Lange syndrome: a case study.

PubMed

Kalal, Goud Iravathy; Raina, Vimarsh P; Nayak, Veerabhadra S; Teotia, Pooja; Gupta, Bhushan V

2009-02-01

Cornelia de Lange syndrome (CDLS) is a relatively common multiple congenital anomaly/mental retardation disorder with an unknown genetic and molecular pathogenesis. The essential features of this developmental malformation syndrome are retardation in growth, developmental delay, various structural limb abnormalities, and distinctive facial features. Most cases are sporadic and are thought to result from a new dominant mutation. Consequently, hypotheses regarding the pathogenetic mechanisms underlying the two distinct phenotypes, classic and mild, are purely speculative. The recent discovery of molecular techniques and identification of the NIPBL gene has allowed etiologic diagnosis of this disorder. In this article, we describe a patient with CDLS in whom conventional cytogenetics, fluorescence in situ hybridization, and NIPBL gene mutation analysis determined an etiologic diagnosis, providing precise genetic counseling and facilitated the family to make an evidence-based decision for conception and also alleviated the extreme degree of anxiety associated with the thought of having a second child in this set of circumstances.

One gene - many endocrine and metabolic syndromes: PTEN-opathies and precision medicine.

PubMed

Yehia, Lamis; Eng, Charis

2018-05-23

An average of 10% of all cancers (range 1-40%) are caused by heritable mutations and over the years, have become powerful models for precision medicine practice. Furthermore, such cancer predisposition genes for seemingly rare syndromes have turned out to help explain mechanisms of sporadic carcinogenesis and often inform normal development. The tumor suppressor PTEN encodes a ubiquitously expressed phosphatase that counteracts the PI3K/AKT/mTOR cascade - one of the most critical growth-promoting signaling pathways. Clinically, individuals with germline PTEN mutations have diverse phenotypes and fall under the umbrella term PTEN hamartoma tumor syndrome (PHTS). PHTS encompasses four clinically distinct allelic overgrowth syndromes, namely Cowden, Bannayan-Riley-Ruvalcaba, Proteus, and Proteus-like syndromes. Relatedly, mutations in other genes encoding components of the PI3K/AKT/mTOR pathway downstream of PTEN also predispose patients to partially overlapping clinical manifestations, with similar effects as PTEN malfunction. We refer to these syndromes as "PTEN-opathies." As a tumor suppressor and key regulator of normal development, PTEN dysfunction can cause a spectrum of phenotypes including benign overgrowths, malignancies, metabolic, and neurodevelopmental disorders. Relevant to clinical practice, the identification of PTEN mutations in patients not only establishes a PHTS molecular diagnosis, but also informs on more accurate cancer risk assessment and medical management of those patients and affected family members. Importantly, timely diagnosis is key, as early recognition allows for preventative measures such as high-risk screening and surveillance even prior to cancer onset. This review highlights the translational impact that the discovery of PTEN has had on the diagnosis, management, and treatment of PHTS.

The role of magnetic resonance imaging in the evaluation of transfusional iron overload in myelodysplastic syndromes.

PubMed

Petrou, Emmanouil; Mavrogeni, Sophie; Karali, Vasiliki; Kolovou, Genovefa; Kyrtsonis, Marie-Christine; Sfikakis, Petros P; Panayiotidis, Panayiotis

2015-01-01

Myelodysplastic syndromes represent a group of heterogeneous hematopoietic neoplasms derived from an abnormal multipotent progenitor cell, characterized by a hyperproliferative bone marrow, dysplasia of the cellular hemopoietic elements and ineffective erythropoiesis. Anemia is a common finding in myelodysplastic syndrome patients, and blood transfusions are the only therapeutic option in approximately 40% of cases. The most serious side effect of regular blood transfusion is iron overload. Currently, cardiovascular magnetic resonance using T2 is routinely used to identify patients with myocardial iron overload and to guide chelation therapy, tailored to prevent iron toxicity in the heart. This is a major validated non-invasive measure of myocardial iron overloading and is superior to surrogates such as serum ferritin, liver iron, ventricular ejection fraction and tissue Doppler parameters. The indication for iron chelation therapy in myelodysplastic syndrome patients is currently controversial. However, cardiovascular magnetic resonance may offer an excellent non-invasive, diagnostic tool for iron overload assessment in myelodysplastic syndromes. Further studies are needed to establish the precise indications of chelation therapy and the clinical implications of this treatment on survival in myelodysplastic syndromes. Copyright © 2014 Associação Brasileira de Hematologia, Hemoterapia e Terapia Celular. Published by Elsevier Editora Ltda. All rights reserved.

Endoscopic laser Doppler flowmetry in the experiment and in the bleeding gastric and duodenal ulcer clinic

NASA Astrophysics Data System (ADS)

Kapralov, S. V.; Shapkin, Y. G.; Lychagov, V. V.; Tuchin, V. V.

2007-05-01

One of the most complex problems of emergency surgery is the choice of surgical tactics to deal with bleeding peptic ulcer. Endoscopic hemostasis is prescribed to patients with continuing bleedings and prerelapse syndrome. But till nowdays the objective verification of the prerelapse condition had not been worked out. What is more there are no objective criteria to judge the effectiveness of the carried endohemostasis. The aim of the study was to work out a new objective diagnostic method of pre-recurrence syndrome that can be able to make prognosis for possible gastroduodenal ulcer bleeding recurrence more precise. Laser Doppler flowmetry was the method of studies the regional perfusion. The device used in this work was made at the Optics and Biophysics Department of Saratov State University.

Identification of novel deletions of 15q11q13 in Angelman syndrome by array-CGH: molecular characterization and genotype-phenotype correlations.

PubMed

Sahoo, Trilochan; Bacino, Carlos A; German, Jennifer R; Shaw, Chad A; Bird, Lynne M; Kimonis, Virginia; Anselm, Irinia; Waisbren, Susan; Beaudet, Arthur L; Peters, Sarika U

2007-09-01

Angelman syndrome (AS) is a neurodevelopmental disorder characterized by mental retardation, absent speech, ataxia, and a happy disposition. Deletions of the 15q11q13 region are found in approximately 70% of AS patients. The deletions are sub-classified into class I and class II based on their sizes of approximately 6.8 and approximately 6.0, respectively, with two different proximal breakpoints and a common distal breakpoint. Utilizing a chromosome 15-specific comparative genomic hybridization genomic microarray (array-CGH), we have identified, determined the deletion sizes, and mapped the breakpoints in a cohort of 44 cases, to relate those breakpoints to the genomic architecture and derive more precise genotype-phenotype correlations. Interestingly four patients of the 44 studied (9.1%) had novel and unusually large deletions, and are reported here. This is the first report of very large deletions of 15q11q13 resulting in AS; the largest deletion being >10.6 Mb. These novel deletions involve three different distal breakpoints, two of which have been earlier shown to be involved in the generation of isodicentric 15q chromosomes (idic15). Additionally, precise determination of the deletion breakpoints reveals the presence of directly oriented low-copy repeats (LCRs) flanking the recurrent and novel breakpoints. The LCRs are adequate in size, orientation, and homology to enable abnormal recombination events leading to deletions and duplications. This genomic organization provides evidence for a common mechanism for the generation of both common and rare deletion types. Larger deletions result in a loss of several genes outside the common Angelman syndrome-Prader-Willi syndrome (AS-PWS) critical interval, and a more severe phenotype.

Carpal Tunnel Syndrome

PubMed Central

Zimmerman, Gregory R.

1994-01-01

Carpal tunnel syndrome is a neuropathy resulting from compression of the median nerve as it passes through a narrow tunnel in the wrist on its way to the hand. The lack of precise objective and clinical tests, along with symptoms that are synonymous with other syndromes in the upper extremity, cause carpal tunnel syndrome to appear to be a rare entity in athletics. However, it should not be ruled out as a possible etiology of upper extremity paralysis in the athlete. More typically, carpal tunnel syndrome is the most common peripheral entrapment neuropathy encountered in industry. Treatment may include rest and/or splinting of the involved wrist, ice application, galvanic stimulation, or iontophoresis to reduce inflammation, and then transition to heat modalities and therapeutic exercises for developing flexibility, strength, and endurance. In addition, an ergonomic assessment should be conducted, resulting in modifications to accommodate the carpal tunnel syndrome patient. ImagesFig 3.Fig 4.Fig 5.Fig 6.Fig 7. PMID:16558255

Disconnection syndromes of basal ganglia, thalamus, and cerebrocerebellar systems.

PubMed

Schmahmann, Jeremy D; Pandya, Deepak N

2008-09-01

Disconnection syndromes were originally conceptualized as a disruption of communication between different cerebral cortical areas. Two developments mandate a re-evaluation of this notion. First, we present a synopsis of our anatomical studies in monkey elucidating principles of organization of cerebral cortex. Efferent fibers emanate from every cortical area, and are directed with topographic precision via association fibers to ipsilateral cortical areas, commissural fibers to contralateral cerebral regions, striatal fibers to basal ganglia, and projection subcortical bundles to thalamus, brainstem and/or pontocerebellar system. We note that cortical areas can be defined by their patterns of subcortical and cortical connections. Second, we consider motor, cognitive and neuropsychiatric disorders in patients with lesions restricted to basal ganglia, thalamus, or cerebellum, and recognize that these lesions mimic deficits resulting from cortical lesions, with qualitative differences between the manifestations of lesions in functionally related areas of cortical and subcortical nodes. We consider these findings on the basis of anatomical observations from tract tracing studies in monkey, viewing them as disconnection syndromes reflecting loss of the contribution of subcortical nodes to the distributed neural circuits. We introduce a new theoretical framework for the distributed neural circuits, based on general, and specific, principles of anatomical organization, and on the architecture of the nodes that comprise these systems. We propose that neural architecture determines function, i.e., each architectonically distinct cortical and subcortical area contributes a unique transform, or computation, to information processing; anatomically precise and segregated connections between nodes define behavior; and association fiber tracts that link cerebral cortical areas with each other enable the cross-modal integration required for evolved complex behaviors. This model enables the formulation and testing of future hypotheses in investigations using evolving magnetic resonance imaging techniques in humans, and in clinical studies in patients with cortical and subcortical lesions.

A Model for Precise and Uniform Pelvic- and Limb-Sparing Abdominal Irradiation to Study the Radiation-Induced Gastrointestinal Syndrome in Mice Using Small Animal Irradiation Systems.

PubMed

Brodin, N Patrik; Velcich, Anna; Guha, Chandan; Tomé, Wolfgang A

2017-01-01

Currently, no readily available mitigators exist for acute abdominal radiation injury. Here, we present an animal model for precise and homogenous limb-sparing abdominal irradiation (LSAIR) to study the radiation-induced gastrointestinal syndrome (RIGS). The LSAIR technique was developed using the small animal radiation research platform (SARRP) with image guidance capabilities. We delivered LSAIR at doses between 14 and 18 Gy on 8- to 10-week-old male C57BL/6 mice. Histological analysis was performed to confirm that the observed mortality was due to acute abdominal radiation injury. A steep dose-response relationship was found for survival, with no deaths seen at doses below 16 Gy and 100% mortality at above 17 Gy. All deaths occurred between 6 and 10 days after irradiation, consistent with the onset of RIGS. This was further confirmed by histological analysis showing clear differences in the number of regenerative intestinal crypts between animals receiving sublethal (14 Gy) and 100% lethal (18 Gy) radiation. The developed LSAIR technique provides uniform dose delivery with a clear dose response, consistent with acute abdominal radiation injury on histological examination. This model can provide a useful tool for researchers investigating the development of mitigators for accidental or clinical high-dose abdominal irradiation.

7-Tesla Magnetic Resonance Imaging Precisely and Noninvasively Reflects Inflammation and Remodeling of the Skeletal Muscle in a Mouse Model of Antisynthetase Syndrome

PubMed Central

Sciorati, Clara; Esposito, Antonio; Campana, Lara; Canu, Tamara; Monno, Antonella; Palmisano, Anna; De Cobelli, Francesco; Del Maschio, Alessandro; Ascheman, Dana P.; Manfredi, Angelo A.; Rovere-Querini, Patrizia

2014-01-01

Inflammatory myopathies comprise heterogeneous disorders. Their etiopathogenesis is poorly understood, because of the paucity of informative experimental models and of approaches for the noninvasive study of inflamed tissues. Magnetic resonance imaging (MRI) provides information about the state of the skeletal muscle that reflects various facets of inflammation and remodeling. This technique has been scarcely used in experimental models of inflammatory myopathies. We characterized the performance of MRI in a well-established mouse model of myositis and the antisynthetase syndrome, based on the immunization of wild-type mice with the amino-terminal fragment of histidyl-tRNA synthetase (HisRS). Over an eight-week period following myositis induction, MRI enabled precise identification of pathological events taking place in muscle tissue. Areas of edema and of active inflammation identified by histopathology paralleled muscle modifications detected noninvasively by MRI. Muscles changes were chronologically associated with the establishment of autoimmunity, as reflected by the development of anti-HisRS antibodies in the blood of immunized mice. MR imaging easily appreciated muscle damage and remodeling even if actual disruption of myofiber integrity (as assessed by serum concentrations of creatinine phosphokinase) was limited. Thus, MR imaging represents an informative and noninvasive analytical tool for studying in vivo immune-mediated muscle involvement. PMID:24895622

The effect of Valerian root extract on the severity of pre menstrual syndrome symptoms.

PubMed

Behboodi Moghadam, Zahra; Rezaei, Elham; Shirood Gholami, Roghaieh; Kheirkhah, Masomeh; Haghani, Hamid

2016-07-01

Premenstrual syndrome (PMS) is a common disorder. Due to the knowledge lack of the precise etiology of this syndrome, different treatment methods are recommended, one of them is the use of medicinal herbs. This study aimed to investigate the effect of Valerian ( xié cǎo) root extract on the intensity of PMS symptoms. In this double-blind clinical trial, 100 female students of Islamic Azad University, Tonekabon Branch, Mazandaran Province, Iran, with PMS were randomly divided into groups receiving Valerian (scientific name: Valeriana officinalis) and placebo in 2013. The participants received 2 pills daily in the last seven days of their menstrual cycle for 3 cycles and recorded their symptoms. The data collection tools included demographic information questionnaire, daily symptom severity questionnaire, and a provisional diagnosis of premenstrual syndrome questionnaire. Data were compared previous, one, two, and three cycles after student's intervention using and analyzed by independent t-test, paired t-test, chi-squared test, and repeated measures ANOVA in SPSS 16. A significant difference was seen in mean emotional, behavioral and physical premenstrual symptom severity in the intervention group before and after the intervention (P < 0.001). However, this difference was not statistically significant in the control group. The results of this study showed that Valerian root extract may reduce emotional, physical, and behavioral symptoms of premenstrual syndrome.

Clinical Characterization of Adults with Asperger's Syndrome Assessed by Self-Report Questionnaires Based on Depression, Anxiety, and Personality

ERIC Educational Resources Information Center

Kanai, Chieko; Iwanami, Akira; Hashimoto, Ryuichiro; Ota, Haruhisa; Tani, Masayuki; Yamada, Takashi; Kato, Nobumasa

2011-01-01

Diagnosing Asperger's syndrome (AS) in adults is difficult and efficient indicators for a precise diagnosis are important in the clinical setting. We examined the clinical characteristics of AS in 129 adults (median age, 32.0 years [range, 19-57]; 102 men and 27 women; AS group (n = 64; median age, 32.0 years [range, 19-50]; 50 men and 14 women),…

Scapulothoracic bursitis and snapping scapula syndrome: a critical review of current evidence.

PubMed

Warth, Ryan J; Spiegl, Ulrich J; Millett, Peter J

2015-01-01

Symptomatic scapulothoracic disorders, such as painful scapular crepitus and/or bursitis, are uncommon; however, they can produce significant pain and disability in many patients. To review the current knowledge pertaining to snapping scapula syndrome and to identify areas of further research that may be helpful to improve clinical outcomes and patient satisfaction. Systematic review. We performed a preliminary search of the PubMed and Embase databases using the search terms "snapping scapula," "scapulothoracic bursitis," "partial scapulectomy," and "superomedial angle resection" in September 2013. All nonreview articles related to the topic of snapping scapula syndrome were included. The search identified a total of 167 unique articles, 81 of which were relevant to the topic of snapping scapula syndrome. There were 36 case series of fewer than 10 patients, 16 technique papers, 11 imaging studies, 9 anatomic studies, and 9 level IV outcomes studies. The level of evidence obtained from this literature search was inadequate to perform a formal systematic review or meta-analysis. Therefore, a critical review of current evidence is presented. Snapping scapula syndrome, a likely underdiagnosed condition, can produce significant shoulder dysfunction in many patients. Because the precise origin is typically unknown, specific treatments that are effective for some patients may not be effective for others. Nevertheless, bursectomy with or without partial scapulectomy is currently the most effective primary method of treatment in patients who fail nonoperative therapy. However, many patients experience continued shoulder disability even after surgical intervention. Future studies should focus on identifying the modifiable factors associated with poor outcomes after operative and nonoperative management for snapping scapula syndrome in an effort to improve clinical outcomes and patient satisfaction. © 2014 The Author(s).

Genetics Home Reference: CHOPS syndrome

MedlinePlus

... complex (SEC) and MLL in development and disease. Genes Dev. 2011 Apr 1;25(7):661-72. doi: 10.1101/gad.2015411. Review. Citation ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Genetics Home Reference: Muckle-Wells syndrome

MedlinePlus

... a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has ... is direct-to-consumer genetic testing? What are genome editing and CRISPR-Cas9? What is precision medicine? ...

Pooling job physical exposure data from multiple independent studies in a consortium study of carpal tunnel syndrome

PubMed Central

Kapellusch, Jay M.; Garg, Arun; Bao, Stephen S.; Silverstein, Barbara A.; Burt, Susan E.; Dale, Ann Marie; Evanoff, Bradley A.; Gerr, Frederic E.; Harris-Adamson, Carisa; Hegmann, Kurt T.; Merlino, Linda A.; Rempel, David M.

2015-01-01

Pooling data from different epidemiological studies of musculoskeletal disorders (MSDs) is necessary to improve statistical power and to more precisely quantify exposure–response relationships for MSDs. The pooling process is difficult and time-consuming, and small methodological differences could lead to different exposure–response relationships. A subcommittee of a six-study research consortium studying carpal tunnel syndrome: (i) visited each study site, (ii) documented methods used to collect physical exposure data and (iii) determined compatibility of exposure variables across studies. Certain measures of force, frequency of exertion and duty cycle were collected by all studies and were largely compatible. A portion of studies had detailed data to investigate simultaneous combinations of force, frequency and duration of exertions. Limited compatibility was found for hand/wrist posture. Only two studies could calculate compatible Strain Index scores, but Threshold Limit Value for Hand Activity Level could be determined for all studies. Challenges of pooling data, resources required and recommendations for future researchers are discussed. PMID:23697792

Potential role of retinoids in ovarian physiology and pathogenesis of polycystic ovary syndrome.

PubMed

Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu

2017-06-01

Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS. Copyright © 2017. Published by Elsevier B.V.

Genetic syndromes associated with overgrowth in childhood

PubMed Central

2013-01-01

Overgrowth syndromes comprise a diverse group of conditions with unique clinical, behavioral and molecular genetic features. While considerable overlap in presentation sometimes exists, advances in identification of the precise etiology of specific overgrowth disorders continue to improve clinicians' ability to make an accurate diagnosis. Among them, this paper introduces two classic genetic overgrowth syndromes: Sotos syndrome and Beckwith-Wiedemann syndrome. Historically, the diagnosis was based entirely on clinical findings. However, it is now understood that Sotos syndrome is caused by a variety of molecular genetic alterations resulting in haploinsufficiency of the NSD1 gene at chromosome 5q35 and that Beckwith-Wiedemann syndrome is caused by heterogeneous abnormalities in the imprinting of a number of growth regulatory genes within chromosome 11p15 in the majority of cases. Interestingly, the 11p15 imprinting region is also associated with Russell-Silver syndrome which is a typical growth retardation syndrome. Opposite epigenetic alterations in 11p15 result in opposite clinical features shown in Beckwith-Wiedemann syndrome and Russell-Silver syndrome. Although the exact functions of the causing genes have not yet been completely understood, these overgrowth syndromes can be good models to clarify the complex basis of human growth and help to develop better-directed therapies in the future. PMID:24904861

Genetics Home Reference: SOX2 anophthalmia syndrome

MedlinePlus

... and sequence variants in the SOX2 and CHX10 genes in patients with anophthalmia/microphthalmia. Mol Vis. 2008 Mar 24;14:583-92. ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Genetics Home Reference: Werner syndrome

MedlinePlus

... a role in natural ageing? Int J Biochem Cell Biol. 2005 May;37(5):947-60. Epub 2004 Dec 15. Review. Citation on ... are genome editing and CRISPR-Cas9? What is precision medicine? What is newborn ...

Genetics Home Reference: familial cold autoinflammatory syndrome

MedlinePlus

... a site of injury or disease to fight microbial invaders and facilitate tissue repair. When this has ... is direct-to-consumer genetic testing? What are genome editing and CRISPR-Cas9? What is precision medicine? ...

Asperger's syndrome in adulthood.

PubMed

Roy, Mandy; Dillo, Wolfgang; Emrich, Hinderk M; Ohlmeier, Martin D

2009-01-01

Asperger's syndrome is one of the autism spectrum disorders. Affected individuals display considerably impaired capacity for social interaction, unusual special interests, and a tendency towards ritualized behavior. The etiology, symptoms, diagnosis, and treatment of Asperger's syndrome in adulthood are outlined on the basis of a selective literature review via Medline and information in relevant reference books. Furthermore, the authors report their personal experience at a special clinic for adults. Asperger's syndrome in adulthood can be diagnosed by thorough anamnesis, heteroanamnesis-with emphasis on childhood-and painstaking clinical examination. The considerable psychosocial impairments affect the patients' professional, social, and private lives. The precise etiology is still unknown, but a multifactorial origin with genetic, neurobiological, and psychosocial components appears probable. Although no specific, empirically tested treatment concepts have yet been established, psychotherapeutic elements (structuring and directive interventions) seem to be helpful, together with pharmacotherapy-if indicated-in the presence of comorbidity. Asperger's syndrome should be included in the differential diagnosis of adults who display the corresponding symptoms. The etiopathogenesis and treatment of Asperger's syndrome in adulthood should be further investigated.

Relationship between the oral cavity and cardiovascular diseases and metabolic syndrome

PubMed Central

Carramolino-Cuéllar, Esther; Tomás, Inmaculada

2014-01-01

The components of the human body are closely interdependent; as a result, disease conditions in some organs or components can influence the development of disease in other body locations. The effect of oral health upon health in general has been investigated for decades by many epidemiological studies. In this context, there appears to be a clear relationship between deficient oral hygiene and different systemic disorders such as cardiovascular disease and metabolic syndrome. The precise relationship between them is the subject of ongoing research, and a variety of theories have been proposed, though most of them postulate the mediation of an inflammatory response. This association between the oral cavity and disease in general requires further study, and health professionals should be made aware of the importance of adopting measures destined to promote correct oral health. The present study conducts a Medline search with the purpose of offering an update on the relationship between oral diseases and cardiovascular diseases, together with an evaluation of the bidirectional relationship between metabolic syndrome and periodontal disease. Most authors effectively describe a moderate association between the oral cavity and cardiovascular diseases, though they also report a lack of scientific evidence that oral alterations constitute an independent cause of cardiovascular diseases, or that their adequate treatment can contribute to prevent such diseases. In the case of metabolic syndrome, obesity and particularly diabetes mellitus may be associated to an increased susceptibility to periodontitis. However, it is not clear whether periodontal treatment is able to improve the systemic conditions of these patients. Key words:Cardiovascular diseases, periodontitis, metabolic syndrome, obesity, diabetes mellitus. PMID:24121926

Space Flight-Associated Neuro-ocular Syndrome.

PubMed

Lee, Andrew G; Mader, Thomas H; Gibson, C Robert; Tarver, William

2017-09-01

New and unique physiologic and pathologic systemic and neuro-ocular responses have been documented in astronauts during and after long-duration space flight. Although the precise cause remains unknown, space flight-associated neuro-ocular syndrome (SANS) has been adopted as an appropriate descriptive term. The Space Medicine Operations Division of the US National Aeronautics and Space Administration (NASA) has documented the variable occurrence of SANS in astronauts returning from long-duration space flight on the International Space Station. These clinical findings have included unilateral and bilateral optic disc edema, globe flattening, choroidal and retinal folds, hyperopic refractive error shifts, and nerve fiber layer infarcts. The clinical findings of SANS have been correlated with structural changes on intraorbital and intracranial magnetic resonance imaging and in-flight and terrestrial ultrasonographic studies and ocular optical coherence tomography. Further study of SANS is ongoing for consideration of future manned missions to space, including a return trip to the moon or Mars.

Genetics Home Reference: Birt-Hogg-Dubé syndrome

MedlinePlus

... B, Schmidt LS. Expression of Birt-Hogg-Dubé gene mRNA in normal and neoplastic human tissues. Mod Pathol. 2004 Aug;17(8):998-1011. ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

Advances in understanding behavioral phenotypes in neurogenetic syndromes.

PubMed

Harris, James C

2010-11-15

Syndrome-specific behavior was proposed by Langdon Down in his first clinical descriptions. Research interest followed but waned during the eugenics era when antisocial behavior was attributed to people with intellectual disability (ID) and the US Supreme Court legalized involuntary sterilization. When these claims were refuted and behavioral treatments introduced, their focus on environmental determination minimized the importance of biological research. The modern era began with the recognition that patterned behavior, for example, self-injury in Lesch-Nyhan syndrome and hyperphagia in PWS, was syndrome-specific, and when parent support groups pointed out syndrome-specific behavioral similarities in their children. Syndrome-specific rating scales and methodologies followed to allow behavioral comparisons between syndromes. The focus initially was on specific behaviors but with refinements in neuropsychological tests has expanded to include neurocognitive profiles. Greater clarification in genetic diagnoses has led to mutant mouse behavioral models and neurophysiologic and neuroimaging strategies have made possible the study of brain circuits. There is growing interest in investigating the developmental trajectory of behaviors from infancy to adulthood and old age. Because anxiety, mood disturbance, repetitive behaviors, and social deficits commonly occur in people with severe ID, those affected are often given multiple psychiatric diagnoses. This has led to considerable confusion in the literature. It is critical to focus on specific behaviors and cognitive patterns in research and not confuse psychiatric symptoms that lack precise definitions and involve multiple genes, the so-called psychiatric phenotype, with the more specific behavioral phenotype. New treatments based on knowledge of underlying neurobiology call for more fine-grained definition of behavior. © 2010 Wiley-Liss, Inc.

Randomized open-label trial of dextromethorphan in Rett syndrome.

PubMed

Smith-Hicks, Constance L; Gupta, Siddharth; Ewen, Joshua B; Hong, Manisha; Kratz, Lisa; Kelley, Richard; Tierney, Elaine; Vaurio, Rebecca; Bibat, Genila; Sanyal, Abanti; Yenokyan, Gayane; Brereton, Nga; Johnston, Michael V; Naidu, Sakkubai

2017-10-17

To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect. © 2017 American Academy of Neurology.

A human neurodevelopmental model for Williams syndrome.

PubMed

Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

2016-08-18

Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

OBESITY PREVALENCE AND METABOLIC SYNDROME IN A PARK USERS

PubMed Central

de SOUZA, Maíra Danielle Gomes; VILAR, Lucio; de ANDRADE, Cinthia Barbosa; ALBUQUERQUE, Raíssa de Oliveira e; CORDEIRO, Lúcia Helena de Oliveira; CAMPOS, Josemberg Marins; FERRAZ, Álvaro Antônio Bandeira

2015-01-01

Background - Overweight and obesity are associated with metabolic syndrome and abdominal obesity, thereby increasing the risk of type 2 diabetes mellitus and cardiovascular diseases. In Brazil, there are still no precise data on the prevalence of these disorders, especially among individuals who carry out some kind of physical activity in public spaces and there are no education and prevention programs for obesity. Aim: To investigate the prevalence of metabolic syndrome and obesity among park users. Methods: A prospective, cross-sectional, descriptive study was conducted with 619 individuals assessed and stratified by profile according to a specific protocol. The group was characterized as follows: female (50.1%) and mean age =50.6±14.8, with predominance of individuals aged between 50 and 59 years (26.8%) and with higher education (68%) and a household income of between 4 and 10 minimum wages (29.2%). Results: Regular physical exercise was reported by 78% of the individuals and it was found that 70.7% were nevertheless of above normal weight: 45% overweight and 25.7% obese, of whom 20.7% had obesity grade I, 3.9% grade II and 1.1% grade III. The prevalence of metabolic syndrome was 4.3%, mostly in men (6.3%). Arterial hypertension and type 2 diabetes mellitus were detected in 17.8% and 5.5%, respectively. In view of the influence of obesity on the occurrence of type 2 diabetes mellitus and metabolic syndrome, it was found that this association was not significant for the two conditions (p=0.014 and 0.017, respectively). Conclusion : The findings demonstrate a high prevalence of overweight and obesity in the studied population, and metabolic syndrome in 4.3%, despite the fact that 70% reported engaging in regular physical activity. PMID:26537270

Urinary profiling of tryptophan and its related metabolites in patients with metabolic syndrome by liquid chromatography-electrospray ionization/mass spectrometry.

PubMed

Oh, Ji Sun; Seo, Hong Seong; Kim, Kyoung Heon; Pyo, Heesoo; Chung, Bong Chul; Lee, Jeongae

2017-09-01

Tryptophan (Trp) is an essential amino acid that plays an important role in protein synthesis and is a precursor of various substances related to diverse biological functions. An imbalance in Trp metabolites is associated with inflammatory diseases. The accurate and precise measurement of these compounds in biological specimens would provide meaningful information for understanding the biochemical states of various metabolic syndrome-related diseases, such as hyperlipidemia, hypertension, diabetes, and obesity. In this study, we developed a rapid, accurate, and sensitive liquid chromatography-tandem mass spectrometry-based method for the simultaneous targeted analysis of Trp and its related metabolites of the kynurenine (Kyn), serotonin, and tryptamine pathways in urine. The application of the developed method was tested using urine samples after protein precipitation. The detection limits of Trp and its metabolites were in the range of 0.01 to 0.1 μg/mL. The method was successfully validated and applied to urine samples from controls and patients with metabolic syndrome. Our results revealed high concentrations of Kyn, kynurenic acid, xanthurenic acid, and quinolinic acid as well as a high Kyn-to-Trp ratio (KTR) in patients with metabolic syndromes. The levels of urine Kyn and KTR were significantly increased in patients under 60 years old. The profiling of urinary Trp metabolites could be a useful indicator for age-related diseases including metabolic syndrome. ᅟ.

Alagille syndrome with deletion 20p12.2-p12.3 and hypoplastic left heart.

PubMed

Robert, Marie Leema P; Lopez, Tony; Crolla, John; Huang, Shuwen; Owen, Carol; Burvill-Holmes, Lisa; Stumper, Oliver; Turnpenny, Peter D

2007-10-01

We report a male patient born at 37-weeks gestation, weighing 1.885 kg (<0.4th centile). Shortly after birth, he was diagnosed with hypoplastic left heart syndrome for which he underwent a Norwood procedure. Subsequently, he developed problems with failure to thrive and developmental delay. At the age of 4 years his delay in growth and development led to further investigations, which revealed a small de-novo interstitial deletion of chromosome 20p12.2. JAGGED1 haploinsufficiency was confirmed by fluorescence in situ hybridization. Array-comparative genomic hybridization analysis confirmed and quantified an approximate 5.4 Mb interstitial deletion involving the chromosomal region 20p12.2-p12.3. This precise interstitial deletion has not been previously reported. Further clinical evaluation revealed posterior embryotoxon and butterfly vertebrae. He has normal liver function tests, facial features consistent with Alagille syndrome, and mild learning difficulties. To our knowledge this is the first report of Alagille syndrome associated with hypoplastic left heart syndrome.

Resting-state functional connectivity predicts longitudinal pain symptom change in urologic chronic pelvic pain syndrome: a MAPP network study.

PubMed

Kutch, Jason J; Labus, Jennifer S; Harris, Richard E; Martucci, Katherine T; Farmer, Melissa A; Fenske, Sonja; Fling, Connor; Ichesco, Eric; Peltier, Scott; Petre, Bogdan; Guo, Wensheng; Hou, Xiaoling; Stephens, Alisa J; Mullins, Chris; Clauw, Daniel J; Mackey, Sean C; Apkarian, A Vania; Landis, J Richard; Mayer, Emeran A

2017-06-01

Chronic pain symptoms often change over time, even in individuals who have had symptoms for years. Studying biological factors that predict trends in symptom change in chronic pain may uncover novel pathophysiological mechanisms and potential therapeutic targets. In this study, we investigated whether brain functional connectivity measures obtained from resting-state functional magnetic resonance imaging at baseline can predict longitudinal symptom change (3, 6, and 12 months after scan) in urologic chronic pelvic pain syndrome. We studied 52 individuals with urologic chronic pelvic pain syndrome (34 women, 18 men) who had baseline neuroimaging followed by symptom tracking every 2 weeks for 1 year as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We found that brain functional connectivity can make a significant prediction of short-term (3 month) pain reduction with 73.1% accuracy (69.2% sensitivity and 75.0% precision). In addition, we found that the brain regions with greatest contribution to the classification were preferentially aligned with the left frontoparietal network. Resting-state functional magnetic resonance imaging measures seemed to be less informative about 6- or 12-month symptom change. Our study provides the first evidence that future trends in symptom change in patients in a state of chronic pain may be linked to functional connectivity within specific brain networks.

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome

PubMed Central

Whittaker, Danielle E.; Kasah, Sahrunizam; Donovan, Alex P. A.; Ellegood, Jacob; Riegman, Kimberley L. H.; Volk, Holger A.; McGonnell, Imelda; Lerch, Jason P.

2017-01-01

Mutations in the gene encoding the ATP dependent chromatin‐remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital‐urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio‐temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. PMID:29168327

Quantitative indexes of aminonucleoside-induced nephrotic syndrome.

PubMed Central

Nevins, T. E.; Gaston, T.; Basgen, J. M.

1984-01-01

Aminonucleoside of puromycin (PAN) is known to cause altered glomerular permeability, resulting in a nephrotic syndrome in rats. The early sequence of this lesion was studied quantitatively, with the application of a new morphometric technique for determining epithelial foot process widths and a sensitive assay for quantifying urinary albumin excretion. Twenty-four hours following a single intraperitoneal injection of PAN, significant widening of foot processes was documented. Within 36 hours significant increases in urinary albumin excretion were observed. When control rats were examined, there was no clear correlation between epithelial foot process width and quantitative albumin excretion. However, in the PAN-treated animals, abnormal albuminuria only appeared in association with appreciable foot process expansion. These studies indicate that quantitative alterations occur in the rat glomerular capillary wall as early as 24 hours after PAN. Further studies of altered glomerular permeability may use these sensitive measures to more precisely define the temporal sequence and elucidate possible subgroups of experimental glomerular injury. Images Figure 1 Figure 2 PMID:6486243

Anti-Műllerian hormone – a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome

PubMed Central

Neagu, M; Cristescu, C

2012-01-01

Background: The anti- Műllerian hormone (AMH) is secreted in women exclusively by the granulosa cells of the ovarian follicles. The serum level of AMH is a precise marker of follicle pool size. In recent clinical studies of polycystic ovary syndrome (PCOS), the serum levels of AMH were elevated about two to threefold. The use of metformin in women with infertility and PCOS has proved to be efficient: restoring ovulation and reducing metabolic dysfunctions. The aim of our study is to assess AMH as a prognostic marker for metformin therapy efficiency in the treatment of women with infertility and polycystic ovary syndrome (PCOS). Methods: Eleven patients with infertility and PCOS were enrolled; PCOS was diagnosed according to the criteria of Androgen Excess and Polycystic Ovarian Syndrome Society 2006 (AE/PCOS). All patients have received metformin therapy. Serum AMH was recorded before and after 2 months of treatment; the normal laboratory values were 2.0-6.8 ng/ml. Results: The primary serum AMH level of all women in study was very high: 8.99±0.99 ng/ml. After 2 months of treatment with metformin ovulation was restored in all the patients and the serum AMH levels were significantly decreased. Conclusions: In clinical practice, serum AMH levels of women with infertility and PCOS receiving metformin are a useful predictive marker for the treatment efficiency. PMID:23346251

Early-Onset Vemurafenib-Induced DRESS Syndrome.

PubMed

Munch, Marion; Peuvrel, Lucie; Brocard, Anabelle; Saint Jean, Mélanie; Khammari, Amir; Dreno, Brigitte; Quereux, Gaelle

2016-01-01

Vemurafenib is a BRAF inhibitor indicated in metastatic or unresectable melanoma in patients with BRAF mutations. Vemurafenib is frequently toxic, but the toxicity is often not serious. The third case of vemurafenib-induced drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is reported herein. The case is unusual in that the onset was early, with symptoms emerging as of day 8 of treatment. Treatment of DRESS syndrome is not currently based on precise recommendations, but systemic corticosteroid therapy is effective in serious cases. Severe toxidermias under vemurafenib are exceptional; immediate discontinuation of treatment upon diagnosis is imperative. Switching from vemurafenib to dabrafenib then seems to constitute an interesting therapeutic alternative, since its efficacy is the same but with fewer cutaneous adverse reactions. This case highlights the importance of awareness of the risk of DRESS syndrome associated with vemurafenib and monitoring for warning signs from treatment initiation. © 2015 S. Karger AG, Basel.

[Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura: classification based on molecular etiology and review of recent developments in diagnostics].

PubMed

Prohászka, Zoltán

2008-07-06

Haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are overlapping clinical entities based on historical classification. Recent developments in the unfolding of the pathomechanisms of these diseases resulted in the creation of a molecular etiology-based classification. Understanding of some causative relationships yielded detailed diagnostic approaches, novel therapeutic options and thorough prognostic assortment of the patients. Although haemolytic uremic syndrome and thrombotic thrombocytopenic purpura are rare diseases with poor prognosis, the precise molecular etiology-based diagnosis might properly direct the therapy of the affected patients. The current review focuses on the theoretical background and detailed description of the available diagnostic possibilities, and some practical information necessary for the interpretation of their results.

Premenstrual syndrome and sleep disturbances: Results from the Sao Paulo Epidemiologic Sleep Study.

PubMed

Nicolau, Zaira F M; Bezerra, Andréia G; Polesel, Daniel N; Andersen, Monica L; Bittencourt, Lia; Tufik, Sergio; Hachul, Helena

2018-06-01

The aim of this study is to compare sleep characteristics between women with premenstrual syndrome (PMS) and a control group. The data were extracted from an epidemiologic survey conducted in Sao Paulo (EPISONO), Brazil, which used subjective assessments and objective polysomnography records to analyze subjects' sleep pattern. Subjective questionnaires used in this study were Women's Questionnaire, Pittsburgh Sleep Quality Index, Epworth sleepiness scale, Insomnia Severity Index and the general sleep questionnaire. The presence of PMS was obtained by a direct question in the Women's Questionnaire. The survey included 230 women, of whom 72.6% reported PMS. The PMS group had poorer sleep quality, a higher perception of unrefreshing sleep and more subthreshold insomnia. Participants with PMS had an increased total sleep time recorded by polysomnography and a lower saturation of peripheral oxygen. It is still unkown the mechanism behind PMS and the sleep-wake cycle. In the other hand, it is clear that PMS play a role in sleep, since women with this disorder has a poor quality of sleep and it is not refreshing. Better knowledge about this syndrome and its outcomes can help to improve their well-being and develop more precise therapeutic approaches. Copyright © 2018 Elsevier B.V. All rights reserved.

Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

PubMed Central

Toussirot, Éric; Gaugler, Béatrice; Bouhaddi, Malika; Nguyen, Nhu Uyen; Saas, Philippe; Dumoulin, Gilles

2010-01-01

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined. PMID:21234350

Is apoptosis a massive process in myelodysplastic syndromes?

PubMed

Lepelley, P; Campergue, L; Grardel, N; Preudhomme, C; Cosson, A; Fenaux, P

1996-11-01

We looked for increased apoptosis in fresh bone marrow aspirates in 40 cases of myelodysplastic syndrome (MDS), by detection of DNA fragmentation using TdT incorporation of nucleotides on 3' ends of DNA (TUNEL technique). No DNA laddering was seen. In six cases (15%) the TUNEL technique showed a moderate increase in the percentage of apoptotic cells (2.5-5% in comparison with < 2% in controls). In seven of the 34 patients with normal findings by TUNEL analysis, apoptosis was reanalysed after short-term (18 h) bone marrow culture without inducers of apoptosis. Increased apoptosis was shown in four of the seven cases by morphological analysis and/or the TUNEL technique. Increased apoptosis predominated on erythroblasts in three of them. The percentage of apoptotic cells, however, was < 40% in all samples. Our findings suggest that increased apoptosis can be detected in one half of MDS cases after cell culture. Furthermore, the precise relationship between increased apoptosis of myeloid precursors and cytopenias will have to be more precisely explored in MDS.

Reliability and construct validity of the Spanish version of the 6-item CTS symptoms scale for outcomes assessment in carpal tunnel syndrome.

PubMed

Rosales, Roberto S; Martin-Hidalgo, Yolanda; Reboso-Morales, Luis; Atroshi, Isam

2016-03-03

The purpose of this study was to assess the reliability and construct validity of the Spanish version of the 6-item carpal tunnel syndrome (CTS) symptoms scale (CTS-6). In this cross-sectional study 40 patients diagnosed with CTS based on clinical and neurophysiologic criteria, completed the standard Spanish versions of the CTS-6 and the disabilities of the arm, shoulder and hand (QuickDASH) scales on two occasions with a 1-week interval. Internal-consistency reliability was assessed with the Cronbach alpha coefficient and test-retest reliability with the intraclass correlation coefficient, two way random effect model and absolute agreement definition (ICC2,1). Cross-sectional precision was analyzed with the Standard Error of the Measurement (SEM). Longitudinal precision for test-retest reliability coefficient was assessed with the Standard Error of the Measurement difference (SEMdiff) and the Minimal Detectable Change at 95 % confidence level (MDC95). For assessing construct validity it was hypothesized that the CTS-6 would have a strong positive correlation with the QuickDASH, analyzed with the Pearson correlation coefficient (r). The standard Spanish version of the CTS-6 presented a Cronbach alpha of 0.81 with a SEM of 0.3. Test-retest reliability showed an ICC of 0.85 with a SRMdiff of 0.36 and a MDC95 of 0.7. The correlation between CTS-6 and the QuickDASH was concordant with the a priori formulated construct hypothesis (r 0.69) CONCLUSIONS: The standard Spanish version of the 6-item CTS symptoms scale showed good internal consistency, test-retest reliability and construct validity for outcomes assessment in CTS. The CTS-6 will be useful to clinicians and researchers in Spanish speaking parts of the world. The use of standardized outcome measures across countries also will facilitate comparison of research results in carpal tunnel syndrome.

Understanding COPD-overlap syndromes.

PubMed

Poh, Tuang Yeow; Mac Aogáin, Micheál; Chan, Adrian Kwok Wai; Yii, Anthony Chau Ang; Yong, Valerie Fei Lee; Tiew, Pei Yee; Koh, Mariko Siyue; Chotirmall, Sanjay Haresh

2017-04-01

Chronic obstructive pulmonary disease accounts for a large burden of lung disease. It can 'overlap' with other respiratory diseases including bronchiectasis, fibrosis and obstructive sleep apnea (OSA). While COPD alone confers morbidity and mortality, common features with contrasting clinical outcomes can occur in COPD 'overlap syndromes'. Areas covered: Given the large degree of heterogeneity in COPD, individual variation to treatment is adopted based on its observed phenotype, which in turn overlaps with features of other respiratory disease states such as asthma. This is coined asthma-COPD overlap syndrome ('ACOS'). Other examples of such overlapping clinical states include bronchiectasis-COPD ('BCOS'), fibrosis-COPD ('FCOS') and OSA-COPD ('OCOS'). The objective of this review is to highlight similarities and differences between the COPD-overlap syndromes in terms of risk factors, pathophysiology, diagnosis and potential treatment differences. Expert commentary: As a consequence of COPD overlap syndromes, a transition from the traditional 'one size fits all' treatment approach is necessary. Greater treatment stratification according to clinical phenotype using a precision medicine approach is now required. In this light, it is important to recognize and differentiate COPD overlap syndromes as distinct disease states compared to individual diseases such as asthma, COPD, fibrosis or bronchiectasis.

Upper arm anthropometrics versus DXA scan in survivors of acute respiratory distress syndrome.

PubMed

Chan, Kitty S; Mourtzakis, Marina; Aronson Friedman, Lisa; Dinglas, Victor D; Hough, Catherine L; Ely, E Wesley; Morris, Peter E; Hopkins, Ramona O; Needham, Dale M

2018-04-01

Survivors of acute respiratory distress syndrome (ARDS) experience severe muscle wasting. Upper arm anthropometrics can provide a quick, non-invasive estimate of muscle status, but its accuracy is unknown. This study examines the accuracy of upper arm percent muscle area (UAMA) with reference measures of lean mass from dual energy X-ray absorptiometry (DXA). Data are from 120 ARDS survivors participating in a multicenter national study. Receiver operating characteristic (ROC) curves, by patient sex, demonstrated that UAMA did no better than chance in discriminating low appendicular skeletal muscle mass identified using DXA findings (c-statistics, 6 months: 0.50-0.59, 12 months: 0.54-0.57). Modest correlations of UAMA with DXA measures (whole-body: r = 0.46-0.49, arm-specific: r = 0.50-0.51, p < 0.001) and Bland-Altman plots indicate poor precision. UAMA is not an appropriate screening measure for estimating muscle mass when compared to a DXA reference standard. Alternate screening measures should be evaluated in ARDS survivors.

Metabolic syndrome, diet and exercise.

PubMed

De Sousa, Sunita M C; Norman, Robert J

2016-11-01

Polycystic ovary syndrome (PCOS) is associated with a range of metabolic complications including insulin resistance (IR), obesity, dyslipidaemia, hypertension, obstructive sleep apnoea (OSA) and non-alcoholic fatty liver disease. These compound risks result in a high prevalence of metabolic syndrome and possibly increased cardiovascular (CV) disease. As the cardiometabolic risk of PCOS is shared amongst the different diagnostic systems, all women with PCOS should undergo metabolic surveillance though the precise approach differs between guidelines. Lifestyle interventions consisting of increased physical activity and caloric restriction have been shown to improve both metabolic and reproductive outcomes. Pharmacotherapy and bariatric surgery may be considered in resistant metabolic disease. Issues requiring further research include the natural history of PCOS-associated metabolic disease, absolute CV risk and comparative efficacy of lifestyle interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Distinct cerebellar foliation anomalies in a CHD7 haploinsufficient mouse model of CHARGE syndrome.

PubMed

Whittaker, Danielle E; Kasah, Sahrunizam; Donovan, Alex P A; Ellegood, Jacob; Riegman, Kimberley L H; Volk, Holger A; McGonnell, Imelda; Lerch, Jason P; Basson, M Albert

2017-12-01

Mutations in the gene encoding the ATP dependent chromatin-remodeling factor, CHD7 are the major cause of CHARGE (Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital-urinary anomalies, and Ear defects) syndrome. Neurodevelopmental defects and a range of neurological signs have been identified in individuals with CHARGE syndrome, including developmental delay, lack of coordination, intellectual disability, and autistic traits. We previously identified cerebellar vermis hypoplasia and abnormal cerebellar foliation in individuals with CHARGE syndrome. Here, we report mild cerebellar hypoplasia and distinct cerebellar foliation anomalies in a Chd7 haploinsufficient mouse model. We describe specific alterations in the precise spatio-temporal sequence of fissure formation during perinatal cerebellar development responsible for these foliation anomalies. The altered cerebellar foliation pattern in Chd7 haploinsufficient mice show some similarities to those reported in mice with altered Engrailed, Fgf8 or Zic1 gene expression and we propose that mutations or polymorphisms in these genes may modify the cerebellar phenotype in CHARGE syndrome. Our findings in a mouse model of CHARGE syndrome indicate that a careful analysis of cerebellar foliation may be warranted in patients with CHARGE syndrome, particularly in patients with cerebellar hypoplasia and developmental delay. © 2017 The Authors. American Journal of Medical Genetics Part C Published by Wiley Periodicals, Inc.

Targets to treat androgen excess in polycystic ovary syndrome.

PubMed

Luque-Ramírez, Manuel; Escobar-Morreale, Héctor Francisco

2015-01-01

The polycystic ovary syndrome (PCOS) is a common androgen disorder in reproductive-aged women. Excessive biosynthesis and secretion of androgens by steroidogenic tissues is its central pathogenetic mechanism. The authors review the potential targets and new drugs to treat androgen excess in PCOS. Besides our lab's experience, a systematic search (MEDLINE, Cochrane library, ClinicalTriasl.gov, EU Clinical Trials Register and hand-searching) regarding observational studies, randomized clinical trials, systematic reviews, meta-analyses and patents about this topic was performed. PCOS has a heterogeneous clinical presentation. It is unlikely that a single drug would cover all its possible manifestations. Available treatments for androgen excess are not free of side effects that are of particular concern in these women who suffer from cardiometabolic risk even without treatment. A precise characterization of the source of androgen excess must tailor antiandrogenic management in each woman, avoiding undesirable side effects.

Emanuel Miller Lecture: Early Onset Depressions--Meanings, Mechanisms and Processes

ERIC Educational Resources Information Center

Goodyer, Ian M.

2008-01-01

Background: Depressive syndromes in children and adolescents constitute a serious group of mental disorders with considerable risk for recurrence. A more precise understanding of aetiology is necessary to improve treatment and management. Methods: Three neuroactive agents are purported to be involved in the aetiology of these disorders: serotonin,…

[Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge].

PubMed

Schmidt, Stefanie J; Behar, Ayla; Schultze-Lutter, Frauke

2018-03-01

Asperger Syndrome and/or Clinical High Risk of Psychosis? A Differential Diagnostic Challenge This case-study deals with the often difficult differential diagnosis of Asperger syndrome and a clinical high risk state of psychosis, in particular as indicated by attenuated psychotic symptoms, as well as with its therapeutic implications. The presented case is a 10-year old girl, who has not been diagnosed with an autism spectrum disorder before being referred to a specialized center for early detection of psychosis due to possible hallucinatory experiences and delusional ideas. We demonstrate how to perform a context-sensitive differential diagnosis to distinguish between specific interests as well as related behaviors and unusual thought content as well as perceptive abnormalities, between paranoid ideas and biased interpretations of the behaviors of others typical for autism, and between disorganized symptoms and autistic unusual communication and social behavior. The resulting dual diagnoses in our case-study formed the basis for a complex differential indication, which considered both the increased stress vulnerability associated with an increased risk for the development of psychosis as well as the rigid thinking style associated with autism. Our case-report shows that such a precise differential indication can lead to stabilization over the long-term, even in patients with dual diagnoses.

Diagnosis of fetal syndromes by three- and four-dimensional ultrasound: is there any improvement?

PubMed

Barišić, Lara Spalldi; Stanojević, Milan; Kurjak, Asim; Porović, Selma; Gaber, Ghalia

2017-08-28

With all of our present knowledge, high technology diagnostic equipment, electronic databases and other available supporting resources, detection of fetal syndromes is still a challenge for healthcare providers in prenatal as well as in the postnatal period. Prenatal diagnosis of fetal syndromes is not straightforward, and it is a difficult puzzle that needs to be assembled and solved. Detection of one anomaly should always raise a suspicion of the existence of more anomalies, and can be a trigger to investigate further and raise awareness of possible syndromes. Highly specialized software systems for three- and four-dimensional ultrasound (3D/4D US) enabled detailed depiction of fetal anatomy and assessment of the dynamics of fetal structural and functional development in real time. With recent advances in 3D/4D US technology, antenatal diagnosis of fetal anomalies and syndromes shifted from the 2nd to the 1st trimester of pregnancy. It is questionable what can and should be done after the prenatal diagnosis of fetal syndrome. The 3D and 4D US techniques improved detection accuracy of fetal abnormalities and syndromes from early pregnancy onwards. It is not easy to make prenatal diagnosis of fetal syndromes, so tools which help like online integrated databases are needed to increase diagnostic precision. The aim of this paper is to present the possibilities of different US techniques in the detection of some fetal syndromes prenatally.

Recent advances in epilepsy genetics.

PubMed

Orsini, Alessandro; Zara, Federico; Striano, Pasquale

2018-02-22

In last few years there has been rapid increase in the knowledge of epilepsy genetics. Nowadays, it is estimated that genetic epilepsies include over than 30% of all epilepsy syndromes. Several genetic tests are now available for diagnostic purposes in clinical practice. In particular, next-generation sequencing has proven to be effective in revealing gene mutations causing epilepsies in up to a third of the patients. This has lead also to functional studies that have given insight into disease pathophysiology and consequently to the identification of potential therapeutic targets opening the way of precision medicine for epilepsy patients. This minireview is focused on the most recent advances in genetics of epilepsies. We will also overview the modern genomic technologies and illustrate the diagnostic pathways in patients with genetic epilepsies. Finally, the potential implications for a personalized treatment (precision medicine) are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

[Evaluation of the reliability of freight elevator operators].

PubMed

Gosk, A; Borodulin-Nadzieja, L; Janocha, A; Salomon, E

1991-01-01

The study involved 58 workers employed at winding machines. Their reliability was estimated from the results of psychomotoric test precision, condition of the vegetative nervous system, and from the results of psychological tests. The tests were carried out at the laboratory and at the workplaces, with all distractive factors and functional connection of the work process present. We have found that the reliability of the workers may be affected by a variety of factors. Among the winding machine operators, work monotony can lead to "monotony syndrome". Among the signalists , the appreciation of great responsibility can lead to unpredictable and non-adequate reactions. From both groups, persons displaying a lower-than-average precision were isolated. All those persons demonstrated a reckless attitude and the opinion of their superiors about them was poor. Those persons constitute potential risk for the reliable operation of the discussed team.

20-Day Trend of Serum Potassium Changes in Bam Earthquake Victims with Crush Syndrome; a Cross-sectional Study.

PubMed

Safari, Saeed; Najafi, Iraj; Hosseini, Mostafa; Baratloo, Alireza; Yousefifard, Mahmoud; Mohammadi, Hamidreza

2017-01-01

Many of those who survive following an earthquake die in the next phase due to preventable and treatable medical conditions such as hyperkalemia. The present study aimed to evaluate the trend of potassium changes in crush syndrome patients of Bam earthquake. In this retrospective cross-sectional study, using the database of Bam earthquake victims, which were developed by Iranian Society of Nephrology following Bam earthquake, Iran, 2003, the 20-day trend of potassium changes in > 15 years old crush syndrome patients was evaluated. 135 crush syndrome patients with the mean age of 29.9 ± 9.91 years were evaluated (56.3% male). Mean potassium concentration during the first 3 days of admission was 5.6 ± 1.3 mEq/L. On the day of admission, 43.1% (95% CI: 34.0 - 52.2) had normal potassium concentration, 3.4% (95% CI: 0.1 - 6.8) had hypokalemia, and 53.4% (44.3 - 62.6) had hyperkalemia. During 20-day follow-up, 62.3% (95% CI: 66.7-71.9) of the patients had normal potassium. While, 11.5% (95% CI: 9.7-13.3) had hypokalemia and 19.2% (95% CI: 17.0-21.5) had hyperkalemia. As the days of hospitalization increased, prevalence of hyperkalemia decreased while hypokalemia increased. On the 17 th day 21.2% (95% CI: 2.2-39.9) had hypokalemia and 10.5% (95% CI: 0.1 - 24.7) had hyperkalemia. Findings of the present study showed that following urine alkalinization and fluid resuscitation, the prevalence of hyperkalemia reduced, but hypokalemia developed. It seems that the correction of serum potassium level should be accompanied by precise monitoring of intake and output of the patient and prescription of reasonable amount of intravenous fluid.

Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients

PubMed Central

Hoornaert, Kristien P; Vereecke, Inge; Dewinter, Chantal; Rosenberg, Thomas; Beemer, Frits A; Leroy, Jules G; Bendix, Laila; Björck, Erik; Bonduelle, Maryse; Boute, Odile; Cormier-Daire, Valerie; De Die-Smulders, Christine; Dieux-Coeslier, Anne; Dollfus, Hélène; Elting, Mariet; Green, Andrew; Guerci, Veronica I; Hennekam, Raoul C M; Hilhorts-Hofstee, Yvonne; Holder, Muriel; Hoyng, Carel; Jones, Kristi J; Josifova, Dragana; Kaitila, Ilkka; Kjaergaard, Suzanne; Kroes, Yolande H; Lagerstedt, Kristina; Lees, Melissa; LeMerrer, Martine; Magnani, Cinzia; Marcelis, Carlo; Martorell, Loreto; Mathieu, Michèle; McEntagart, Meriel; Mendicino, Angela; Morton, Jenny; Orazio, Gabrielli; Paquis, Véronique; Reish, Orit; Simola, Kalle O J; Smithson, Sarah F; Temple, Karen I; Van Aken, Elisabeth; Van Bever, Yolande; van den Ende, Jenneke; Van Hagen, Johanna M; Zelante, Leopoldo; Zordania, Riina; De Paepe, Anne; Leroy, Bart P; De Buyzere, Marc; Coucke, Paul J; Mortier, Geert R

2010-01-01

Stickler syndrome is an autosomal dominant connective tissue disorder caused by mutations in different collagen genes. The aim of our study was to define more precisely the phenotype and genotype of Stickler syndrome type 1 by investigating a large series of patients with a heterozygous mutation in COL2A1. In 188 probands with the clinical diagnosis of Stickler syndrome, the COL2A1 gene was analyzed by either a mutation scanning technique or bidirectional fluorescent DNA sequencing. The effect of splice site alterations was investigated by analyzing mRNA. Multiplex ligation-dependent amplification analysis was used for the detection of intragenic deletions. We identified 77 different COL2A1 mutations in 100 affected individuals. Analysis of the splice site mutations showed unusual RNA isoforms, most of which contained a premature stop codon. Vitreous anomalies and retinal detachments were found more frequently in patients with a COL2A1 mutation compared with the mutation-negative group (P<0.01). Overall, 20 of 23 sporadic patients with a COL2A1 mutation had either a cleft palate or retinal detachment with vitreous anomalies. The presence of vitreous anomalies, retinal tears or detachments, cleft palate and a positive family history were shown to be good indicators for a COL2A1 defect. In conclusion, we confirm that Stickler syndrome type 1 is predominantly caused by loss-of-function mutations in the COL2A1 gene as >90% of the mutations were predicted to result in nonsense-mediated decay. On the basis of binary regression analysis, we developed a scoring system that may be useful when evaluating patients with Stickler syndrome. PMID:20179744

Preclinical Alterations in the Serum of COL(IV)A3(-)/(-) Mice as Early Biomarkers of Alport Syndrome.

PubMed

Muckova, Petra; Wendler, Sindy; Rubel, Diana; Büchler, Rita; Alert, Mandy; Gross, Oliver; Rhode, Heidrun

2015-12-04

The efficiency of the inhibition of the angiotensin converting enzyme, the most widely used therapy for the Alport syndrome, depends on the onset of the therapy-the earlier the better. Hence, early progressive biomarkers are urgently required to allow for preclinical diagnosis, an early start of possible therapy as well as the monitoring of this therapy. In the present study, an improved comprehensive and precise proteomic approach has been applied to the serum of juvenile Alport-mice, nontreated and treated, and wild-type controls of various ages to search for biomarkers. With a total of 2542 stringently altered proteins, the serum composition clearly shows a dependency on age, that is, stage, and therapy. Initially, the serum constituents indicate an enhanced extracellular matrix remodeling, cell damage, and the production of particular acute phase proteins. A panel of 15 potential biomarker candidates has been identified. In later stages, renal filtration failure and systemic acute phase reaction determine the composition of the serum; an effect that is well-known for manifested human Alport syndrome. With a small number of mouse urine samples, for example, the proteomic results for gelsolin could be verified using ELISA. Once verified in man, these early biomarkers would allow for a sensitive and specific diagnosis of the Alport syndrome in children as well as facilitate the monitoring of a possible therapy.

Fibromyalgia and Myofascial Pain Syndrome-A Dilemma

PubMed Central

Chandola, H C; Chakraborty, Arunangshu

2009-01-01

Summary Pain and fatigue associated to the musculoskeletal system are among the leading causes of patients to visit their physicians and nearly one-third of such patients suffer from fibromyalgia. Fibromyalgia syndrome (FMS) is a chronic debilitating disorder characterized by widespread pain with tenderness in specific areas, leading to fatigue, headache and sleep disorder. Myofascial Pain Syndrome (MPS), is also a localized musculoskeletal pain producing condition whose diagnostic and management criteria differ from FMS but still considered by many only a subtype of FMS. Till date no exact cause has been held responsible for these painful conditions, therefore treatment of these disorders is always a challenge. The therapies are not precise but multimodal including pharmacological and alternative approaches. This article describes the existing knowledge pertaining to these conditions in regard of causative factors diagnosis and management. PMID:20640108

[Epigenome: what we learned from Rett syndrome, a neurological disease caused by mutation of a methyl-CpG binding protein].

PubMed

Kubota, Takeo

2013-01-01

Epigenome is defined as DNA and histone modification-dependent gene regulation system. Abnormalities in this system are known to cause various neuro-developmental diseases. We recently reported that neurological symptoms of Rett syndrome, which is an autistic disorder caused by mutations in methyl-CpG binding protein 2 (MeCP2), was associated with failure of epigenomic gene regulation in neuronal cells, and that clinical differences in the identical twins with Rett syndrome in the differences in DNA methylation in neuronal genes, but not caused by DNA sequence differences. Since central nervus system requires precise gene regulation, neurological diseases including Alzheimer and Parkinson diseases may be caused by acquired DNA modification (epigenomic) changes that results in aberrant gene regulation as well as DNA sequence changes congenitally occurred (mutation).

Disorders of Human Hemoglobin

NASA Astrophysics Data System (ADS)

Bank, Arthur; Mears, J. Gregory; Ramirez, Francesco

1980-02-01

Studies of the human hemoglobin system have provided new insights into the regulation of expression of a group of linked human genes, the γ -δ -β globin gene complex in man. In particular, the thalassemia syndromes and related disorders of man are inherited anemias that provide mutations for the study of the regulation of globin gene expression. New methods, including restriction enzyme analysis and cloning of cellular DNA, have made it feasible to define more precisely the structure and organization of the globin genes in cellular DNA. Deletions of specific globin gene fragments have already been found in certain of these disorders and have been applied in prenatal diagnosis.

Butyric acid in irritable bowel syndrome.

PubMed

Załęski, Andrzej; Banaszkiewicz, Aleksandra; Walkowiak, Jarosław

2013-01-01

Butyric acid (butanoic acid) belongs to a group of short-chain fatty acids and is thought to play several beneficial roles in the gastrointestinal tract. Butyric anion is easily absorbed by enteric cells and used as a main source of energy. Moreover, butyric acid is an important regulator of colonocyte proliferation and apoptosis, gastrointestinal tract motility and bacterial microflora composition in addition to its involvement in many other processes including immunoregulation and anti-inflammatory activity. The pathogenesis of irritable bowel syndrome (IBS), the most commonly diagnosed functional gastrointestinal condition, is complex, and its precise mechanisms are still unclear. This article describes the potential benefits of butyric acid in IBS.

Defining recovery in chronic fatigue syndrome: a critical review.

PubMed

Adamowicz, Jenna L; Caikauskaite, Indre; Friedberg, Fred

2014-11-01

In chronic fatigue syndrome (CFS), the lack of consensus on how recovery should be defined or interpreted has generated controversy and confusion. The purpose of this paper was to systematically review, compare, and evaluate the definitions of recovery reported in the CFS literature and to make recommendations about the scope of recovery assessments. A search was done using the MEDLINE, PubMed, PsycINFO, CINAHL, and Cochrane databases for peer review papers that contained the search terms "chronic fatigue syndrome" and "recovery," "reversal," "remission," and/or "treatment response." From the 22 extracted studies, recovery was operationally defined by reference with one or more of these domains: (1) pre-morbid functioning; (2) both fatigue and function; (3) fatigue (or related symptoms) alone; (4) function alone; and/or (5) brief global assessment. Almost all of the studies measuring recovery in CFS did so differently. The brief global assessment was the most common outcome measure used to define recovery. Estimates of recovery ranged from 0 to 66 % in intervention studies and 2.6 to 62 % in naturalistic studies. Given that the term "recovery" was often based on limited assessments and less than full restoration of health, other more precise and accurate labels (e.g., clinically significant improvement) may be more appropriate and informative. In keeping with common understandings of the term recovery, we recommend a consistent definition that captures a broad-based return to health with assessments of both fatigue and function as well as the patient's perceptions of his/her recovery status.

Genetic and phenotypic dissection of 1q43q44 microdeletion syndrome and neurodevelopmental phenotypes associated with mutations in ZBTB18 and HNRNPU.

PubMed

Depienne, Christel; Nava, Caroline; Keren, Boris; Heide, Solveig; Rastetter, Agnès; Passemard, Sandrine; Chantot-Bastaraud, Sandra; Moutard, Marie-Laure; Agrawal, Pankaj B; VanNoy, Grace; Stoler, Joan M; Amor, David J; Billette de Villemeur, Thierry; Doummar, Diane; Alby, Caroline; Cormier-Daire, Valérie; Garel, Catherine; Marzin, Pauline; Scheidecker, Sophie; de Saint-Martin, Anne; Hirsch, Edouard; Korff, Christian; Bottani, Armand; Faivre, Laurence; Verloes, Alain; Orzechowski, Christine; Burglen, Lydie; Leheup, Bruno; Roume, Joelle; Andrieux, Joris; Sheth, Frenny; Datar, Chaitanya; Parker, Michael J; Pasquier, Laurent; Odent, Sylvie; Naudion, Sophie; Delrue, Marie-Ange; Le Caignec, Cédric; Vincent, Marie; Isidor, Bertrand; Renaldo, Florence; Stewart, Fiona; Toutain, Annick; Koehler, Udo; Häckl, Birgit; von Stülpnagel, Celina; Kluger, Gerhard; Møller, Rikke S; Pal, Deb; Jonson, Tord; Soller, Maria; Verbeek, Nienke E; van Haelst, Mieke M; de Kovel, Carolien; Koeleman, Bobby; Monroe, Glen; van Haaften, Gijs; Attié-Bitach, Tania; Boutaud, Lucile; Héron, Delphine; Mignot, Cyril

2017-04-01

Subtelomeric 1q43q44 microdeletions cause a syndrome associating intellectual disability, microcephaly, seizures and anomalies of the corpus callosum. Despite several previous studies assessing genotype-phenotype correlations, the contribution of genes located in this region to the specific features of this syndrome remains uncertain. Among those, three genes, AKT3, HNRNPU and ZBTB18 are highly expressed in the brain and point mutations in these genes have been recently identified in children with neurodevelopmental phenotypes. In this study, we report the clinical and molecular data from 17 patients with 1q43q44 microdeletions, four with ZBTB18 mutations and seven with HNRNPU mutations, and review additional data from 37 previously published patients with 1q43q44 microdeletions. We compare clinical data of patients with 1q43q44 microdeletions with those of patients with point mutations in HNRNPU and ZBTB18 to assess the contribution of each gene as well as the possibility of epistasis between genes. Our study demonstrates that AKT3 haploinsufficiency is the main driver for microcephaly, whereas HNRNPU alteration mostly drives epilepsy and determines the degree of intellectual disability. ZBTB18 deletions or mutations are associated with variable corpus callosum anomalies with an incomplete penetrance. ZBTB18 may also contribute to microcephaly and HNRNPU to thin corpus callosum, but with a lower penetrance. Co-deletion of contiguous genes has additive effects. Our results confirm and refine the complex genotype-phenotype correlations existing in the 1qter microdeletion syndrome and define more precisely the neurodevelopmental phenotypes associated with genetic alterations of AKT3, ZBTB18 and HNRNPU in humans.

Laser-capture micro dissection combined with next-generation sequencing analysis of cell type-specific deafness gene expression in the mouse cochlea.

PubMed

Nishio, Shin-Ya; Takumi, Yutaka; Usami, Shin-Ichi

2017-05-01

Cochlear implantation (CI), which directly stimulates the cochlear nerves, is the most effective and widely used medical intervention for patients with severe to profound sensorineural hearing loss. The etiology of the hearing loss is speculated to have a major influence of CI outcomes, particularly in cases resulting from mutations in genes preferentially expressed in the spiral ganglion region. To elucidate precise gene expression levels in each part of the cochlea, we performed laser-capture micro dissection in combination with next-generation sequencing analysis and determined the expression levels of all known deafness-associated genes in the organ of Corti, spiral ganglion, lateral wall, and spiral limbs. The results were generally consistent with previous reports based on immunocytochemistry or in situ hybridization. As a notable result, the genes associated with many kinds of syndromic hearing loss (such as Clpp, Hars2, Hsd17b4, Lars2 for Perrault syndrome, Polr1c and Polr1d for Treacher Collins syndrome, Ndp for Norrie Disease, Kal for Kallmann syndrome, Edn3 and Snai2 for Waardenburg Syndrome, Col4a3 for Alport syndrome, Sema3e for CHARGE syndrome, Col9a1 for Sticker syndrome, Cdh23, Cib2, Clrn1, Pcdh15, Ush1c, Ush2a, Whrn for Usher syndrome and Wfs1 for Wolfram syndrome) showed higher levels of expression in the spiral ganglion than in other parts of the cochlea. This dataset will provide a base for more detailed analysis in order to clarify gene functions in the cochlea as well as predict CI outcomes based on gene expression data. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Genetics Home Reference: deafness and myopia syndrome

MedlinePlus

... This Page Aruga J, Yokota N, Mikoshiba K. Human SLITRK family genes: genomic organization and expression profiling in normal brain ... AH. SLITRK6 mutations cause myopia and deafness in humans and mice. J Clin Invest. 2013 May;123(5):2094-102. doi: 10.1172/JCI65853. Epub ... are genome editing and CRISPR-Cas9? What is precision medicine? What ...

mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome.

PubMed

Johnson, Simon C; Yanos, Melana E; Kayser, Ernst-Bernhard; Quintana, Albert; Sangesland, Maya; Castanza, Anthony; Uhde, Lauren; Hui, Jessica; Wall, Valerie Z; Gagnidze, Arni; Oh, Kelly; Wasko, Brian M; Ramos, Fresnida J; Palmiter, Richard D; Rabinovitch, Peter S; Morgan, Philip G; Sedensky, Margaret M; Kaeberlein, Matt

2013-12-20

Mitochondrial dysfunction contributes to numerous health problems, including neurological and muscular degeneration, cardiomyopathies, cancer, diabetes, and pathologies of aging. Severe mitochondrial defects can result in childhood disorders such as Leigh syndrome, for which there are no effective therapies. We found that rapamycin, a specific inhibitor of the mechanistic target of rapamycin (mTOR) signaling pathway, robustly enhances survival and attenuates disease progression in a mouse model of Leigh syndrome. Administration of rapamycin to these mice, which are deficient in the mitochondrial respiratory chain subunit Ndufs4 [NADH dehydrogenase (ubiquinone) Fe-S protein 4], delays onset of neurological symptoms, reduces neuroinflammation, and prevents brain lesions. Although the precise mechanism of rescue remains to be determined, rapamycin induces a metabolic shift toward amino acid catabolism and away from glycolysis, alleviating the buildup of glycolytic intermediates. This therapeutic strategy may prove relevant for a broad range of mitochondrial diseases.

The Potential of iPSCs for the Treatment of Premature Aging Disorders

PubMed Central

Compagnucci, Claudia; Bertini, Enrico

2017-01-01

Premature aging disorders including Hutchinson-Gilford progeria syndrome (HGPS) and Werner syndrome, are a group of rare monogenic diseases leading to reduced lifespan of the patients. Importantly, these disorders mimic several features of physiological aging. Despite the interest on the study of these diseases, the underlying biological mechanisms remain unknown and no treatment is available. Recent studies on HGPS (due to mutations of the LMNA gene encoding for the nucleoskeletal proteins lamin A/C) have reported disruptions in cellular and molecular mechanisms modulating genomic stability and stem cell populations, thus giving the nuclear lamina a relevant function in nuclear organization, epigenetic regulation and in the maintenance of the stem cell pool. In this context, modeling premature aging with induced pluripotent stem cells (iPSCs) offers the possibility to study these disorders during self-renewal and differentiation into relevant cell types. iPSCs generated by cellular reprogramming from adult somatic cells allows researchers to understand pathophysiological mechanisms and enables the performance of drug screenings. Moreover, the recent development of precision genome editing offers the possibility to study the complex mechanisms underlying senescence and the possibility to correct disease phenotypes, paving the way for future therapeutic interventions. PMID:29112121

The Application of Root Mean Square Electrocardiography (RMS ECG) for the Detection of Acquired and Congenital Long QT Syndrome

PubMed Central

Lux, Robert L.; Sower, Christopher Todd; Allen, Nancy; Etheridge, Susan P.; Tristani-Firouzi, Martin; Saarel, Elizabeth V.

2014-01-01

Background Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS). Methods RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. Results All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. Conclusion These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements. PMID:24454918

The application of root mean square electrocardiography (RMS ECG) for the detection of acquired and congenital long QT syndrome.

PubMed

Lux, Robert L; Sower, Christopher Todd; Allen, Nancy; Etheridge, Susan P; Tristani-Firouzi, Martin; Saarel, Elizabeth V

2014-01-01

Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RTPK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS). RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RTPK, QTRMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II. All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3. These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements.

Whole-exome sequencing identifies USH2A mutations in a pseudo-dominant Usher syndrome family.

PubMed

Zheng, Sui-Lian; Zhang, Hong-Liang; Lin, Zhen-Lang; Kang, Qian-Yan

2015-10-01

Usher syndrome (USH) is an autosomal recessive (AR) multi-sensory degenerative disorder leading to deaf-blindness. USH is clinically subdivided into three subclasses, and 10 genes have been identified thus far. Clinical and genetic heterogeneities in USH make a precise diagnosis difficult. A dominant‑like USH family in successive generations was identified, and the present study aimed to determine the genetic predisposition of this family. Whole‑exome sequencing was performed in two affected patients and an unaffected relative. Systematic data were analyzed by bioinformatic analysis to remove the candidate mutations via step‑wise filtering. Direct Sanger sequencing and co‑segregation analysis were performed in the pedigree. One novel and two known mutations in the USH2A gene were identified, and were further confirmed by direct sequencing and co‑segregation analysis. The affected mother carried compound mutations in the USH2A gene, while the unaffected father carried a heterozygous mutation. The present study demonstrates that whole‑exome sequencing is a robust approach for the molecular diagnosis of disorders with high levels of genetic heterogeneity.

Seizures, syndromes, and etiologies in childhood epilepsy: The International League Against Epilepsy 1981, 1989, and 2017 classifications used in a population-based cohort.

PubMed

Aaberg, Kari Modalsli; Surén, Pål; Søraas, Camilla Lund; Bakken, Inger Johanne; Lossius, Morten I; Stoltenberg, Camilla; Chin, Richard

2017-11-01

The study provides updated information about the distribution of seizures, epilepsies, and etiologies of epilepsy in the general child population, and compares the old and new classification systems from the International League Against Epilepsy (ILAE). The study platform was the Norwegian Mother and Child Cohort Study. Cases of epilepsy were identified through registry linkages and sequential parental questionnaires. Epilepsy diagnoses were validated using a standardized protocol, and seizures, epilepsies, and etiologies were classified according to the old (ILAE 1981/1989) and new (ILAE 2017) classifications. Information was collected through medical record reviews and/or parental telephone interviews. The study population included 112,744 children aged 3-13 years at the end of follow-up on December 31, 2012. Of these, there were 606 children with epilepsy (CWE). Distribution of seizure types varied by age of onset. Multiple seizure types were common with early onset. Focal epilepsies were the most common, occurring in 317 per 100,000 children in the study population and in 59% of CWE. Generalized epilepsies were found in 190 per 100,000 (35% of CWE). CWE with onset during the first 2 years of life had an even distribution of focal and generalized epilepsies, whereas focal epilepsies became dominant at later ages of onset. A definite cause of epilepsy had been demonstrated in 33% of CWE. The ILAE 1989 classification allowed for a broad syndrome category in 93% of CWE and a defined epileptic syndrome in 37%. With the ILAE 2017 classification, 41% of CWE had a defined epileptic syndrome and 63% had either a defined syndrome or structural-metabolic etiology. The distribution of seizures and epilepsies is strongly dependent on age of onset. Despite diagnostic advances, the causes of epilepsy are still unknown in two-thirds of CWE. The ILAE 2017 classifications allow for a higher precision of diagnoses, but at the expense of leaving more epilepsies classifiable only at the mode of onset level. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Creatine metabolism: detection of creatine and guanidinoacetate in saliva of healthy subjects.

PubMed

Martínez, Lidia D; Bezard, Miriam; Brunotto, Mabel; Dodelson de Kremer, Raquel

2016-04-01

Creatine (Cr) plays an important role in storage and transmission of phosphate-bound energy. Cerebral creatine deficiency syndromes comprise three inherited defects in Cr biosynthesis and transport. The aim of this study was to investigate whether Cr and Guanidinoacetate (GAA) can be detected in saliva of healthy subjects and to establish the relationship between salivary and plasma levels of these molecules. An adapted gas chromatography (GC) method is described for the quantification of Cr and GAA biomarkers in saliva. Reference values were established for GAA and Cr in saliva. These values were age dependent (p= 0.001). No difference between genders was observed. We detected a difference between GAA and Cr concentrations in saliva and in plasma. The GC method for simultaneous determination of GAA and Cr in human saliva is fast, reliable, sensitive, non-invasive and precise to use as a biochemical approach in early detection of cerebral creatine deficiency syndromes. Sociedad Argentina de Investigación Odontológica.

Development of real-time PCR assays for the detection of Moraxella macacae associated with bloody nose syndrome in rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques

PubMed Central

Whitehouse, Chris A.; Chase, Kitty; Embers, Monica E.; Kulesh, David A.; Ladner, Jason T.; Palacios, Gustavo F.; Minogue, Timothy D.

2016-01-01

Background Moraxella macacae is a recently described bacterial pathogen that causes epistaxis or so-called bloody nose syndrome in captive macaques. The aim of this study was to develop specific molecular diagnostic assays for M. macacae and to determine their performance characteristics. Methods We developed six real-time PCR assays on the Roche LightCycler. The accuracy, precision, selectivity, and limit of detection (LOD) were determined for each assay, in addition to further validation by testing nasal swabs from macaques presenting with epistaxis at the Tulane National Primate Research Center. Results All assays exhibited 100% specificity and were highly sensitive with an LOD of 10 fg for chromosomal assays and 1 fg for the plasmid assay. Testing of nasal swabs from 10 symptomatic macaques confirmed the presence of M. macacae in these animals. Conclusions We developed several accurate, sensitive, and species-specific real-time PCR assays for the detection of M. macacae in captive macaques. PMID:26365904

Treatment alternatives of congenital hand differences with thumb hypoplasia involvement.

PubMed

Papadogeorgou, Ellada V; Soucacos, Panayotis N

2008-01-01

Congenital thumb hypoplasia is a complex and heterogeneous congenital difference that is detrimental to hand function. Apart from its' classic form, which is now considered to be part of radial dysplasia, it can occur as part of other congenital anomalies including, syndactyly, symbrachydactyly, atypical cleft hand, bifid thumb, triphalangeal thumb, mirror hand, constriction band syndrome, as well as generalized anomalies and syndromes. Management is aimed primarily at restoring basic hand function, specifically, power grasp and precision pinch, and secondarily to improve cosmoses, which inevitably is going to be impaired. Several treatment alternatives have been proposed to manage the specific disabling condition and include, 1st web space reconstruction and opponensplasty, pollicization, toe-to-hand transfer, distraction lengthening, free toe phalangeal transfer or the use of allograft, stabilization of the metacarpophalangeal joint, and surgery of "spare parts." The purpose of this study is to evaluate the various alternatives available today and propose an algorithm applicable for the appropriate management of thumb deficiency, based on their specific characteristics. Copyright 2008 Wiley-Liss, Inc. Microsurgery, 2008.

What does the nature of the MECP2 mutation tell us about parental origin and recurrence risk in Rett syndrome?

PubMed

Zhang, J; Bao, X; Cao, G; Jiang, S; Zhu, X; Lu, H; Jia, L; Pan, H; Fehr, S; Davis, M; Leonard, H; Ravine, D; Wu, X

2012-12-01

The MECP2 mutations occurring in the severe neurological disorder Rett syndrome are predominantly de novo, with rare familial cases. The aims of this study were to provide a precise estimate of the parental origin of MECP2 mutations using a large Chinese sample and to assess whether parental origin varied by mutation type. The parental origin was paternal in 84/88 [95.5%, (95% confidence interval 88.77-98.75)] of sporadic Chinese cases. However, in a pooled sample including data from the literature the spectrum of mutations occurring on maternally and paternally derived chromosomes differed significantly. The excess we found of 'single base pair gains or losses' on maternally derived MECP2 gene alleles suggests that this mutational category is associated with an elevated risk of gonadal mosaicism, which has implications for genetic counseling. © 2011 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

Prediction of Cerebral Hyperperfusion Syndrome with Velocity Blood Pressure Index.

PubMed

Lai, Zhi-Chao; Liu, Bao; Chen, Yu; Ni, Leng; Liu, Chang-Wei

2015-06-20

Cerebral hyperperfusion syndrome is an important complication of carotid endarterectomy (CEA). An >100% increase in middle cerebral artery velocity (MCAV) after CEA is used to predict the cerebral hyperperfusion syndrome (CHS) development, but the accuracy is limited. The increase in blood pressure (BP) after surgery is a risk factor of CHS, but no study uses it to predict CHS. This study was to create a more precise parameter for prediction of CHS by combined the increase of MCAV and BP after CEA. Systolic MCAV measured by transcranial Doppler and systematic BP were recorded preoperatively; 30 min postoperatively. The new parameter velocity BP index (VBI) was calculated from the postoperative increase ratios of MCAV and BP. The prediction powers of VBI and the increase ratio of MCAV (velocity ratio [VR]) were compared for predicting CHS occurrence. Totally, 6/185 cases suffered CHS. The best-fit cut-off point of 2.0 for VBI was identified, which had 83.3% sensitivity, 98.3% specificity, 62.5% positive predictive value and 99.4% negative predictive value for CHS development. This result is significantly better than VR (33.3%, 97.2%, 28.6% and 97.8%). The area under the curve (AUC) of receiver operating characteristic: AUC(VBI) = 0.981, 95% confidence interval [CI] 0.949-0.995; AUC(VR) = 0.935, 95% CI 0.890-0.966, P = 0.02. The new parameter VBI can more accurately predict patients at risk of CHS after CEA. This observation needs to be validated by larger studies.

Challenging Behavior in Smith-Lemli-Opitz Syndrome: Initial Test of Biobehavioral Influences

PubMed Central

Freeman, Kurt A.; Eagle, Rose; Merkens, Louise S.; Sikora, Darryn; Pettit-Kekel, Kersti; Nguyen-Driver, Mina; Steiner, Robert D.

2013-01-01

Objective To study challenging behavior (destruction, aggression, self-injury, stereotypy) in children with Smith-Lemli-Opitz syndrome (SLOS) using a biobehavioral model that helps distinguish biological from socially mediated variables influencing the behavior. Background SLOS is an autosomal-recessive syndrome of multiple malformations and intellectual disability resulting from a genetic error in cholesterol synthesis in all cells and tissues, including brain. The exact cause of the challenging behavior in SLOS is unclear, but defective brain cholesterol synthesis may contribute. Because the precise genetic and biochemical etiology of SLOS is known, this disorder is a good model for studying biological causes of challenging behavior. Method In a preliminary application of a biobehavioral model, we studied the association between cholesterol levels (as a biochemical indicator of disease severity) and behavior subtype (“biological” vs “learned”) in 13 children with SLOS. Parents completed a questionnaire that categorized challenging behavior as influenced primarily by social or nonsocial (thus, presumably biological) factors. Results The severity of the cholesterol synthesis defect correlated significantly with behavior subtype classification for 1 of 2 challenging behaviors. Greater severity of the cholesterol synthesis defect was associated with behavior being classified as primarily influenced by biological factors. Conclusion The interplay between challenging behavior and defective cholesterol synthesis in SLOS may help explain biological influences on the behavior. Our findings have implications for research on the effectiveness of behavioral and medical treatments for behavioral difficulties in SLOS and other neurodevelopmental disorders. PMID:23538569

Mastitis associated with Sjögren's syndrome: a series of nine cases.

PubMed

Goulabchand, Radjiv; Hafidi, Assia; Millet, Ingrid; Morel, Jacques; Lukas, Cédric; Humbert, Sébastien; Rivière, Sophie; Gény, Christian; Jorgensen, Christian; Le Quellec, Alain; Perrochia, Hélène; Guilpain, Philippe

2017-02-01

Sjögren's syndrome is well known to target exocrine glands, especially lacrimal and salivary glands, which share with mammary glands anatomical, histological, and immunological features. Herein, we investigated the mammary involvement in patients with Sjögren's syndrome and compared the histological findings with minor salivary gland involvement. We reviewed the charts of patients with Sjögren's syndrome (followed in Montpellier University Hospital, between January 2000 and January 2015), in whom minor salivary gland and mammary tissues were available. Two expert pathologists analysed retrospectively these tissues in order to identify inflammatory patterns. Immunohistochemical stainings were performed to precise leucocyte distribution. Sixteen Sjögren's syndrome patients with available salivary and breast tissue samples were included. All were women, with a median age of 60.1 ± 11.3 years at Sjögren's syndrome diagnosis. Mammary biopsy was conducted because of breast symptoms in 6 patients and following imaging screening strategies for breast cancer in 10 patients. Nine patients exhibited an inflammatory breast pattern (lymphocytic infiltrates or duct ectasia), close to minor salivary gland histological findings. Immunohistochemical stainings (n = 5) revealed B and T cell infiltrates within breast tissue, with a higher proportion of T CD4+ cells, but no IgG4-secreting plasma cells were found. This is the first series to describe breast inflammatory patterns in Sjögren's syndrome. Mastitis is in line with the classical involvement of exocrine glands in this disease. These findings are consistent with the literature data considering Sjögren's syndrome as an "autoimmune epithelitis".

Revised estimates of the risk of fetal loss following a prenatal diagnosis of trisomy 13 or trisomy 18.

PubMed

Cavadino, Alana; Morris, Joan K

2017-04-01

Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) both have high natural fetal loss rates. The aim of this study was to provide estimates of these fetal loss rates by single gestational week of age using data from the National Down Syndrome Cytogenetic Register. Data from all pregnancies with Edwards or Patau syndrome that were prenatally detected in England and Wales from 2004 to 2014 was analyzed using Kaplan-Meier survival estimates. Pregnancies were entered into the analysis at the time of gestation at diagnosis, and were considered "under observation" until the gestation at outcome. There were 4088 prenatal diagnoses of trisomy 18 and 1471 of trisomy 13 in the analysis. For trisomy 18, 30% (95%CI: 25-34%) of viable fetuses at 12 weeks will result in a live birth and at 39 weeks gestation 67% (60-73%) will result in a live birth. For trisomy 13 the survival is 50% (41-58%) at 12 weeks and 84% (73-90%) at 39 weeks. There was no significant difference in survival between males and females when diagnosed at 12 weeks for trisomy 18 (P-value = 0.27) or trisomy 13 (P-value = 0.47). This paper provides the most precise gestational age-specific estimates currently available for the risk of fetal loss in trisomy 13 and trisomy 18 pregnancies in a general population. © 2017 Wiley Periodicals, Inc.

Posttreatment Lyme disease syndrome.

PubMed

Aucott, John N

2015-06-01

The prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. Risk factors include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Optimal treatment of PTLDS awaits more precise understanding of the pathophysiologic mechanisms involved in this illness and future treatment trials. Copyright © 2015 Elsevier Inc. All rights reserved.

Periventricular heterotopia in a boy with interstitial deletion of chromosome 4p.

PubMed

Gawlik-Kuklinska, Katarzyna; Wierzba, Jolanta; Wozniak, Agnieszka; Iliszko, Mariola; Debiec-Rychter, Maria; Dubaniewicz-Wybieralska, Miroslawa; Limon, Janusz

2008-01-01

We report on a 4-year-old boy with a proximal interstitial deletion in the short arm of chromosome 4p with the karyotype 46,XY,del(4)(p14p15.32),inv(9)(p13q13). For a precise delineation of the deleted region, an array-based comparative genomic hybridization (a-CGH) analysis was performed. The proband's phenotype and cytogenetic findings are compared with previously reported cases with proximal 4p deletion syndrome. The syndrome is associated with normal growth, varying degrees of mental retardation, characteristic facial appearance and minor dysmorphic features. Additionally, our patient developed a seizure disorder due to abnormal neuronal migration, i.e., periventricular heterotopia.

Applying Precision Medicine to Trial Design Using Physiology. Extracorporeal CO2 Removal for Acute Respiratory Distress Syndrome.

PubMed

Goligher, Ewan C; Amato, Marcelo B P; Slutsky, Arthur S

2017-09-01

In clinical trials of therapies for acute respiratory distress syndrome (ARDS), the average treatment effect in the study population may be attenuated because individual patient responses vary widely. This inflates sample size requirements and increases the cost and difficulty of conducting successful clinical trials. One solution is to enrich the study population with patients most likely to benefit, based on predicted patient response to treatment (predictive enrichment). In this perspective, we apply the precision medicine paradigm to the emerging use of extracorporeal CO 2 removal (ECCO 2 R) for ultraprotective ventilation in ARDS. ECCO 2 R enables reductions in tidal volume and driving pressure, key determinants of ventilator-induced lung injury. Using basic physiological concepts, we demonstrate that dead space and static compliance determine the effect of ECCO 2 R on driving pressure and mechanical power. This framework might enable prediction of individual treatment responses to ECCO 2 R. Enriching clinical trials by selectively enrolling patients with a significant predicted treatment response can increase treatment effect size and statistical power more efficiently than conventional enrichment strategies that restrict enrollment according to the baseline risk of death. To support this claim, we simulated the predicted effect of ECCO 2 R on driving pressure and mortality in a preexisting cohort of patients with ARDS. Our computations suggest that restricting enrollment to patients in whom ECCO 2 R allows driving pressure to be decreased by 5 cm H 2 O or more can reduce sample size requirement by more than 50% without increasing the total number of patients to be screened. We discuss potential implications for trial design based on this framework.

Precise detection of chromosomal translocation or inversion breakpoints by whole-genome sequencing.

PubMed

Suzuki, Toshifumi; Tsurusaki, Yoshinori; Nakashima, Mitsuko; Miyake, Noriko; Saitsu, Hirotomo; Takeda, Satoru; Matsumoto, Naomichi

2014-12-01

Structural variations (SVs), including translocations, inversions, deletions and duplications, are potentially associated with Mendelian diseases and contiguous gene syndromes. Determination of SV-related breakpoints at the nucleotide level is important to reveal the genetic causes for diseases. Whole-genome sequencing (WGS) by next-generation sequencers is expected to determine structural abnormalities more directly and efficiently than conventional methods. In this study, 14 SVs (9 balanced translocations, 1 inversion and 4 microdeletions) in 9 patients were analyzed by WGS with a shallow (5 × ) to moderate read coverage (20 × ). Among 28 breakpoints (as each SV has two breakpoints), 19 SV breakpoints had been determined previously at the nucleotide level by any other methods and 9 were uncharacterized. BreakDancer and Integrative Genomics Viewer determined 20 breakpoints (16 translocation, 2 inversion and 2 deletion breakpoints), but did not detect 8 breakpoints (2 translocation and 6 deletion breakpoints). These data indicate the efficacy of WGS for the precise determination of translocation and inversion breakpoints.

Monogenic and chromosomal causes of isolated speech and language impairment.

PubMed

Barnett, C P; van Bon, B W M

2015-11-01

The importance of a precise molecular diagnosis for children with intellectual disability, autism spectrum disorder and epilepsy has become widely accepted and genetic testing is an integral part of the diagnostic evaluation of these children. In contrast, children with an isolated speech or language disorder are not often genetically evaluated, despite recent evidence supporting a role for genetic factors in the aetiology of these disorders. Several chromosomal copy number variants and single gene disorders associated with abnormalities of speech and language have been identified. Individuals without a precise genetic diagnosis will not receive optimal management including interventions such as early testosterone replacement in Klinefelter syndrome, otorhinolaryngological and audiometric evaluation in 22q11.2 deletion syndrome, cardiovascular surveillance in 7q11.23 duplications and early dietary management to prevent obesity in proximal 16p11.2 deletions. This review summarises the clinical features, aetiology and management options of known chromosomal and single gene disorders that are associated with speech and language pathology in the setting of normal or only mildly impaired cognitive function. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Detection of VR-2332 strain of porcine reproductive and respiratory syndrome virus type II using an aptamer-based sandwich-type assay.

PubMed

Lee, Su Jin; Kwon, Young Seop; Lee, Ji-eun; Choi, Eun-Jin; Lee, Chang-Hee; Song, Jae-Young; Gu, Man Bock

2013-01-02

Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine reproductive and respiratory syndrome disease (PRRS), a disease that has a significant and economic impact on the swine industry. In this study, single-stranded DNA (ssDNA) aptamers with high specificity and affinity against VR-2332 strain of PRRSV type II were successfully obtained. Of 19 candidates, the LB32 aptamer was found to be the most specific and sensitive to VR-2332 strain according to an aptamer-based surface plasmon resonance (SPR) analysis. The detection of VR-2332 of PRRSV type II was successfully accomplished using the enzyme-linked antibody-aptamer sandwich (ELAAS) method. The detection limit of ELAAS was 4.8 × 10(0) TCID(50)/mL that is comparable to some of the previous reports of the PCR-based detection but does not require any complicated equipment or extra costs. Moreover, this ELAAS-based PRRSV detection showed similar sensitivity for both the VR-2332 samples spiked in diluted swine serum and in buffer. Therefore, this VR-2332 strain-specific aptamer and its assay method with high specificity can be used as an alternative method for the fast and precise detection of PRRSV.

Analyses of Genotypes and Phenotypes of Ten Chinese Patients with Wolf-Hirschhorn Syndrome by Multiplex Ligation-dependent Probe Amplification and Array Comparative Genomic Hybridization

PubMed Central

Yang, Wen-Xu; Pan, Hong; Li, Lin; Wu, Hai-Rong; Wang, Song-Tao; Bao, Xin-Hua; Jiang, Yu-Wu; Qi, Yu

2016-01-01

Background: Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome that is typically caused by a deletion of the distal portion of the short arm of chromosome 4. However, there are few reports about the features of Chinese WHS patients. This study aimed to characterize the clinical and molecular cytogenetic features of Chinese WHS patients using the combination of multiplex ligation-dependent probe amplification (MLPA) and array comparative genomic hybridization (array CGH). Methods: Clinical information was collected from ten patients with WHS. Genomic DNA was extracted from the peripheral blood of the patients. The deletions were analyzed by MLPA and array CGH. Results: All patients exhibited the core clinical symptoms of WHS, including severe growth delay, a Greek warrior helmet facial appearance, differing degrees of intellectual disability, and epilepsy or electroencephalogram anomalies. The 4p deletions ranged from 2.62 Mb to 17.25 Mb in size and included LETM1, WHSC1, and FGFR3. Conclusions: The combined use of MLPA and array CGH is an effective and specific means to diagnose WHS and allows for the precise identification of the breakpoints and sizes of deletions. The deletion of genes in the WHS candidate region is closely correlated with the core WHS phenotype. PMID:26960370

[Renal biopsy findings in diabetes mellitus].

PubMed

Kharrat, Mahmoud; Kammoun, Khawala; Charfeddine, Khaled; Yaich, Soumaya; Zaghdene, Saoussen; Chaker, Hanene; Jarraya, Faiçal; Ben Hmida, Mohamed; Jlidi, Rachid; Hachicha, Jamil

2007-03-01

The prevalence of diabetic patients with endstage renal disease is increased overall the word. Renal biopsy is sometimes necessary to precise the type of renal damage. To precise the type and the frequency of non diabetic nephropathy in diabetic patients. We enrolled retrospectively during 17 years, 72 diabetic patients who had a renal biopsy. A non diabetic nephropathy was found in 69.5 % of them. Its presence was correlate to the presence of hematuria and the absence of diabetic retinopathy. We can successfully treated nine patients with minimal-change nephrotic syndrome and one patient with crescentic glomerulonephritis. Renal biopsy must be done in diabetic patient with hematuria or in the absence of diabetic retinopathy.

Needle placement for piriformis injection using 3-D imaging.

PubMed

Clendenen, Steven R; Candler, Shawn A; Osborne, Michael D; Palmer, Scott C; Duench, Stephanie; Glynn, Laura; Ghazi, Salim M

2013-01-01

Piriformis syndrome is a pain syndrome originating in the buttock and is attributed to 6% - 8% of patients referred for the treatment of back and leg pain. The treatment for piriformis syndrome using fluoroscopy, computed tomography (CT), electromyography (EMG), and ultrasound (US) has become standard practice. The treatment of Piriformis Syndrome has evolved to include fluoroscopy and EMG with CT guidance. We present a case study of 5 successful piriformis injections using 3-D computer-assisted electromagnet needle tracking coupled with ultrasound. A 6-degree of freedom electromagnetic position tracker was attached to the ultrasound probe that allowed the system to detect the position and orientation of the probe in the magnetic field. The tracked ultrasound probe was used to find the posterior superior iliac spine. Subsequently, 3 points were captured to register the ultrasound image with the CT or magnetic resonance image scan. Moreover, after the registration was obtained, the navigation system visualized the tracked needle relative to the CT scan in real-time using 2 orthogonal multi-planar reconstructions centered at the tracked needle tip. Conversely, a recent study revealed that fluoroscopically guided injections had 30% accuracy compared to ultrasound guided injections, which tripled the accuracy percentage. This novel technique exhibited an accurate needle guidance injection precision of 98% while advancing to the piriformis muscle and avoiding the sciatic nerve. The mean (± SD) procedure time was 19.08 (± 4.9) minutes. This technique allows for electromagnetic instrument tip tracking with real-time 3-D guidance to the selected target. As with any new technique, a learning curve is expected; however, this technique could offer an alternative, minimizing radiation exposure.

Relationship of neuromotor disturbances to psychosis symptoms in first-episode neuroleptic-naive schizophrenia patients.

PubMed

Cortese, Leonardo; Caligiuri, Michael P; Malla, Ashok K; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

2005-06-01

From the very inception of the modern diagnostic scheme for psychotic disorders, abnormalities in motor function have been observed in these conditions. Despite convergence from multiple areas of research supporting the notion that multiple frontal-subcortical circuits regulate motor and limbic behavior, the precise relationship between motor abnormalities and psychopathology has not been elucidated. The goals of this study were to examine the prevalence of extrapyramidal signs (EPS) in first-episode schizophrenia patients and their relationships to three psychopathological dimensions (positive psychosis syndrome, negative syndrome, and disorganization). We assessed EPS using traditional observer-based as well as quantitative instrumental measures in 39 neuroleptic-naive first-episode schizophrenia subjects. Subjects were followed for 6 months after initiating antipsychotic treatment to examine the stability of motor-limbic relationships. Four main findings emerged from this study. First, depending on the measure used the prevalence of dyskinesia prior to treatment ranged from 13% to 20%. The prevalence of parkinsonism ranged from 18% to 28%. Second, severity of dyskinesia was associated with the positive psychotic syndrome; whereas parkinsonism was associated with the positive psychosis, negative syndrome and disorganization. Third, psychopathology improved significantly across all symptom dimensions following antipsychotic treatment, while EPS remained stable. This suggests that some motor abnormalities in schizophrenia may reflect trait characteristics. Fourth, abnormalities on the pre-treatment instrumental measure of parkinsonism predicted greater improvement on positive psychosis symptoms following treatment (p=0.008). Our findings support the notion that neuromotor disturbances may be a core feature of schizophrenia in a substantial proportion of patients and implicate multiple fronto-striatal circuits regulating limbic and neuromotor behavior in schizophrenia.

Guillain-Barré Syndrome, variants & forms fruste: Reclassification with new criteria.

PubMed

Hiew, Fu Liong; Ramlan, Rahmansah; Viswanathan, Shanthi; Puvanarajah, Santhi

2017-07-01

This study aimed to evaluate the clinical and electrophysiological characteristics of various distinctive classical and localised Guillain-Barré syndrome (GBS) subtypes. Clinical characteristics and electrophysiological data of sixty-one consecutive patients admitted between 2012 and 2015 were systematically analysed and reclassified according to the new GBS clinical classification. Neurophysiology was evaluated with Hadden et al.'s vs recently proposed Rajabally et al.'s criteria. Functional severity and clinical outcome of various GBS subtypes were ascertained. All patients initially identified as GBS or related disorders can be sub-classified into having classical GBS (41, 67%), classic Miller-Fisher Syndrome (MFS) (6, 10%), Pharyngeal-cervical-brachial (PCB) (3, 5%), paraparetic GBS (4, 7%), bifacial weakness with paresthesia (3, 5%), acute ophthalmoparesis (AO) (1, 2%) and overlap syndrome (3, 5%): one (2%) with GBS/Bickerstaff brainstem encephalitis overlap and 2 (3%) with GBS/MFS overlap. Greater proportion of axonal classical GBS (67% vs 55%, p=0.372) seen with Rajabally et al.'s criteria and a predominantly axonal form of paraparetic variant (75%) independent of electrodiagnostic criteria were more representative of Asian GBS cohort. Classical GBS patients had lowest admission and discharge Medical Research Council Sum Score (MRCSS), greater functional disability and longest length of in-patient stay. Twenty (20/21, 95%) patients who needed mechanical ventilation had classical GBS. Patients required repeated dose of intravenous immunoglobulin (5/6, 3%) or plasma exchange (4/4, 100%) more frequently had axonal form of classical GBS. Phenotype recognition based on new GBS clinical classification, supported by electrodiagnostic study permits more precise clinical subtypes determination and outcome prognostication. Copyright © 2017 Elsevier B.V. All rights reserved.

Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria.

PubMed

Yildiz, Bulent Okan; Bozdag, Gurkan; Yapici, Zuhal; Esinler, Ibrahim; Yarali, Hakan

2012-10-01

What is the prevalence, phenotype and metabolic features of polycystic ovary syndrome (PCOS) in the same population according to three different diagnostic criteria? The prevalence of PCOS under National Institutes of Health (NIH), Rotterdam and Androgen Excess and PCOS (AE-PCOS) Society criteria was 6.1, 19.9 and 15.3%, respectively. PCOS carried a 2-fold increased risk of metabolic syndrome regardless of the diagnostic criteria used. The prevalence rates of PCOS differ depending on the diagnostic criteria used to define the syndrome. The current paper gives the prevalence rates of the component and composite phenotypes of PCOS in the same population and reports similar rates of metabolic syndrome in women with PCOS under contrasting diagnostic criteria. In this cross-sectional study, 392 women between the ages of 18 and 45 years were analyzed. When the prevalence of PCOS according to NIH was set to 8% with a precision of 2.2% and confidence interval of 95%, the sample size required for a prevalence survey was found to be 400 subjects. The study was carried out in the General Directorate of Mineral Research and Exploration, a government-based institute, in which the largest number of female staff (n = 527) are employed within a single institute in Ankara, Turkey. The study was performed between 7 December 2009 and 30 April 2010. All female subjects between the ages of 18 and 45 years were invited to participate. Women older than 45 or younger than 18 years, post-menopausal women, women with a history of hysterectomy or bilateral oopherectomy and pregnant women were excluded. Totally, 392 of the employees were recruited for the final analyses. The prevalence of PCOS under NIH, Rotterdam and AE-PCOS Society criteria were 6.1, 19.9 and 15.3%, respectively. While the prevalence of metabolic syndrome was 6.1% in the whole study group, within the patients diagnosed as PCOS according to NIH, Rotterdam and AE-PCOS Society criteria, it was 12.5, 10.3 and 10.0%, respectively. Even though we have included women working at a single institution with a high response rate for the participation, we cannot exclude potential selection bias due to undetermined differences between our sample and background community. We might have underestimated actual prevalence of metabolic syndrome in PCOS due to lack of oral glucose tolerance test 2 h glucose data. Current results can be generalized to Caucasian populations and may present variations in other populations according to race and ethnicity. This work was, in part, sponsored by Merck Serono. Not applicable.

Cloning of the breakpoints of a de novo inversion of chromosome 8, inv (8)(p11.2q23.1) in a patient with Ambras syndrome.

PubMed

Tadin-Strapps, M; Warburton, D; Baumeister, F A M; Fischer, S G; Yonan, J; Gilliam, T C; Christiano, A M

2004-01-01

Ambras syndrome (AMS) is a unique form of universal congenital hypertrichosis. In patients with this syndrome, the whole body is covered with fine long hair, except for areas where normally no hair grows. There is accompanying facial dysmorphism and teeth abnormalities, including retarded first and second dentition and absence of teeth. In 1993, Baumeister et al. reported an isolated case of Ambras syndrome in association with a pericentric inversion of chromosome 8. Subsequently, another patient with congenital hypertrichosis and rearrangement of chromosome 8 was reported by Balducci et al. (1998). Both of these patients have a breakpoint in 8q22 in common suggesting that this region of chromosome 8 contains a gene involved in regulation of hair growth. In order to precisely determine the nature of the rearrangement in the case of Ambras syndrome, we have used fluorescent in situ hybridization (FISH) analysis. We have cloned the inversion breakpoints in this patient and generated a detailed physical map of the inversion breakpoint interval. Analysis of the transcripts that map in the vicinity of the breakpoints revealed that the inversion does not disrupt a gene, and suggests that the phenotype is caused by a position effect. Copyright 2004 S. Karger AG, Basel

Effects of curcumin consumption on human chronic diseases: A narrative review of the most recent clinical data.

PubMed

Mantzorou, Maria; Pavlidou, Eleni; Vasios, George; Tsagalioti, Eftychia; Giaginis, Constantinos

2018-06-01

Numerous clinical trials have investigated the potential beneficial effects of curcumin supplementation against several human chronic diseases. Up to now, it has been claimed that curcumin consumption may exert beneficial effects against several chronic diseases by promoting human health and preventing diseases. In this aspect, the present review aims to critically collect and in-depth summarize the most recent, well-designed clinical studies evaluating the potential beneficial effects of curcumin consumption on human health promotion and disease prevention. According to recent and well-designed clinical studies, curcumin consumption may benefit against obesity, metabolic syndrome, and diabetes. Moreover, curcumin consumption seems to exert a positive effect on people suffering from various types of cancer, fatty liver disease, depression, arthritis, skin diseases, gut inflammation, and symptoms of premenstrual syndrome. Due to the strong heterogeneity among the clinical studies concerning the exact effective curcumin dose and formulation, as well as the recommended treatment duration for each chronic disease, no precise and definitive conclusions could be drawn. Further large-scale prospective studies are strongly recommended, being well-designed as far as follow-up times, dosage, formulation, and duration of curcumin supplementation are concerned. Moreover, potential confounders in each specific chronic disease should carefully be taken into account in future studies. Copyright © 2018 John Wiley & Sons, Ltd.

Spectrum of glomerulonephritides in adults with nephrotic syndrome in Pakistan.

PubMed

Kazi, Javed Iqbal; Mubarak, Muhammed; Ahmed, Ejaz; Akhter, Fazal; Naqvi, Syed Ali Anwer; Rizvi, Syed Adeebul Hassan

2009-02-01

There is currently little information in literature about the pattern of glomerulonephritides (GN) in adults with nephrotic syndrome in this part of the world, particularly that involving the use of immunofluorescence (IMF) and electron microscopy (EM). A few studies reported are based on light microscopic study alone and hence do not reflect the true pattern of GN underlying nephrotic syndrome. We carried out this study in the Department of Histopathology, Sindh Institute of Urology and Transplantation (SIUT), Karachi, Pakistan to determine, for the first time, the true pattern of GN in adult nephrotic patients from Pakistan. SIUT is a tertiary care center for renal and urologic disease in Pakistan. The Histopathology Laboratory of SIUT is equipped with all the modalities, including EM, required for precise diagnosis of glomerular disease. This is a retrospective clinicopathologic study involving retrieval of clinical and pathological data from a review of original renal biopsy reports of adult patients with nephrotic syndrome who presented at the adult nephrology clinic of SIUT from July 1996 till July 2006. Two cores of renal tissue were routinely obtained. One core was fixed in 10% buffered formalin and processed for light microscopy; the other core was divided into two halves, for EM and the IMF study. A total of 316 adult patients were included. Of these, 201 (63.6%) were male and 115 (36.4%) were female. Mean age was 28.4 +/- 10.51 years with a range of 16-78 years. The spectrum of pathological lesions in the adult nephrotic population was wide and comprised focal segmental glomerulosclerosis (FSGS) (39.87%), followed by membranous GN (MGN) (26.58%), minimal change disease (MCD) (14.82%), mesangiocapillary GN (4.3%), mesangioproliferative GN (4.11%), post-infectious GN (2.84%), IgA nephropathy (2.53%), and other rare lesions. Results from this study indicate that FSGS is the single most common cause of nephrotic syndrome in adult nephrotic patients, followed by MGN, and MCD. Our data are similar to those reported in recent series from the US. The study defines the pattern of glomerular disease in adult nephrotic patients for the first time in this region, because it is based on light microscopy, serology, IMF, and EM findings.

SCN5A (NaV1.5) Variant Functional Perturbation and Clinical Presentation: Variants of a Certain Significance.

PubMed

Kroncke, Brett M; Glazer, Andrew M; Smith, Derek K; Blume, Jeffrey D; Roden, Dan M

2018-05-01

Accurately predicting the impact of rare nonsynonymous variants on disease risk is an important goal in precision medicine. Variants in the cardiac sodium channel SCN5A (protein Na V 1.5; voltage-dependent cardiac Na+ channel) are associated with multiple arrhythmia disorders, including Brugada syndrome and long QT syndrome. Rare SCN5A variants also occur in ≈1% of unaffected individuals. We hypothesized that in vitro electrophysiological functional parameters explain a statistically significant portion of the variability in disease penetrance. From a comprehensive literature review, we quantified the number of carriers presenting with and without disease for 1712 reported SCN5A variants. For 356 variants, data were also available for 5 Na V 1.5 electrophysiological parameters: peak current, late/persistent current, steady-state V1/2 of activation and inactivation, and recovery from inactivation. We found that peak and late current significantly associate with Brugada syndrome ( P <0.001; ρ=-0.44; Spearman rank test) and long QT syndrome disease penetrance ( P <0.001; ρ=0.37). Steady-state V1/2 activation and recovery from inactivation associate significantly with Brugada syndrome and long QT syndrome penetrance, respectively. Continuous estimates of disease penetrance align with the current American College of Medical Genetics classification paradigm. Na V 1.5 in vitro electrophysiological parameters are correlated with Brugada syndrome and long QT syndrome disease risk. Our data emphasize the value of in vitro electrophysiological characterization and incorporating counts of affected and unaffected carriers to aid variant classification. This quantitative analysis of the electrophysiological literature should aid the interpretation of Na V 1.5 variant electrophysiological abnormalities and help improve Na V 1.5 variant classification. © 2018 American Heart Association, Inc.

Do patients with symptoms and signs of lower urinary tract dysfunction need a urodynamic diagnosis? ICI-RS 2013.

PubMed

Rosier, Peter F W M; Giarenis, Ilias; Valentini, Francoise A; Wein, Alan; Cardozo, Linda

2014-06-01

The ICI-RS Think Tank discussed the diagnostic process for patients who present with symptoms and signs of lower urinary tract (LUT) dysfunction. This manuscript reflects the Think Tank's summary and opinion. An overview of the existing evidence and consensus regarding urodynamic testing was presented and discussed in relation to contemporary treatment strategies. Evidence of the validity of the diagnostic process in relation to the contemporary management paradigm is incomplete, scattered, and sometimes conflicting and therefore a process redesign may be necessary. The Think Tanks' suggestion, contained in this manuscript, is that the symptoms and signs that the patients present can be more precisely delineated as syndromes. The overactive bladder syndrome (OAB-S); the stress urinary incontinence syndrome (SUI-S); the urinary incontinence syndrome (UI-S); the voiding dysfunction syndrome (VD-S); and or the neurogenic LUT dysfunction syndrome (NLUTD-S) may become evidence based starting point for initial management. Consistent addition of the word syndrome, if adequately defined, acknowledges the uncertainty, but will improve outcome and will improve selection of patients that need further (invasive) diagnosis before management. The ICS-RS Think Tank has summarized the level of evidence for UDS and discussed the evidence in association with the currently changing management paradigm. The ICI-RS Think Tank recommends that the diagnostic process for patients with LUTD can be redesigned. Carefully delineated and evidence based LUTD syndromes may better indicate, personalize and improve the outcome of initial management, and may also contribute to improved and rational selection of patients for invasive UDS. Neurourol. Urodynam. 33:581-586, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Demographic, clinical and therapeutic findings in a monocentric cohort of adult patients with suspected PFAPA syndrome.

PubMed

Vitale, Antonio; Orlando, Ida; Lopalco, Giuseppe; Emmi, Giacomo; Cattalini, Marco; Frediani, Bruno; Galeazzi, Mauro; Iannone, Florenzo; Rigante, Donato; Cantarini, Luca

2016-01-01

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenopathy (PFAPA) syndrome is a non-Mendelian autoinflammatory disorder until now considered to be specifically limited to paediatric age. Recently, an increasing number of reports seems to suggest that PFAPA syndrome, diagnosed by the Marshall criteria revised by Thomas et al., can also affect adults. The Marshall/Thomas criteria have been applied to 989 adult patients presenting for recurrent fever episodes: all patients enrolled were reviewed for demographic, clinical, and therapeutic data. Infectious, neoplastic, autoimmune and other autoinflammatory diseases were ruled out. We identified 30 adult patients (19 males, 11 females) with a suspected PFAPA syndrome: their mean age at disease onset was 33.75±14.01 years, mean age at diagnosis 39.1±14.39 years, and mean body temperature peak 39.5±0.7°C. In addition, the mean frequency of febrile episodes was 11.58±8.97 per year. More precisely, patients complained of pharyngitis (77%), cervical adenitis (73%), asthenia (63%), arthralgia (67%), oral aphthosis (50%), myalgia (54%), cephalalgia (43%), abdominal pain (27%), nausea/vomiting (17%), periorbital pain (17%), and arthritis (10%). Six out of 30 (20%) patients had suffered from PFAPA syndrome also during childhood, and the disease had reappeared in adulthood. We provide the largest monocentric cohort of patients diagnosed with a suspected PFAPA syndrome in adulthood confirming that this syndrome can occur also during adulthood; moreover, due to the medical history of our patients and based on our experience, PFAPA syndrome might relapse during adulthood after a temporary remission reached in the course of paediatric age.

Applications of Computer Technology in Complex Craniofacial Reconstruction.

PubMed

Day, Kristopher M; Gabrick, Kyle S; Sargent, Larry A

2018-03-01

To demonstrate our use of advanced 3-dimensional (3D) computer technology in the analysis, virtual surgical planning (VSP), 3D modeling (3DM), and treatment of complex congenital and acquired craniofacial deformities. We present a series of craniofacial defects treated at a tertiary craniofacial referral center utilizing state-of-the-art 3D computer technology. All patients treated at our center using computer-assisted VSP, prefabricated custom-designed 3DMs, and/or 3D printed custom implants (3DPCI) in the reconstruction of craniofacial defects were included in this analysis. We describe the use of 3D computer technology to precisely analyze, plan, and reconstruct 31 craniofacial deformities/syndromes caused by: Pierre-Robin (7), Treacher Collins (5), Apert's (2), Pfeiffer (2), Crouzon (1) Syndromes, craniosynostosis (6), hemifacial microsomia (2), micrognathia (2), multiple facial clefts (1), and trauma (3). In select cases where the available bone was insufficient for skeletal reconstruction, 3DPCIs were fabricated using 3D printing. We used VSP in 30, 3DMs in all 31, distraction osteogenesis in 16, and 3DPCIs in 13 cases. Utilizing these technologies, the above complex craniofacial defects were corrected without significant complications and with excellent aesthetic results. Modern 3D technology allows the surgeon to better analyze complex craniofacial deformities, precisely plan surgical correction with computer simulation of results, customize osteotomies, plan distractions, and print 3DPCI, as needed. The use of advanced 3D computer technology can be applied safely and potentially improve aesthetic and functional outcomes after complex craniofacial reconstruction. These techniques warrant further study and may be reproducible in various centers of care.

Assessing the severity of sleep apnea syndrome based on ballistocardiogram

PubMed Central

Zhou, Xingshe; Zhao, Weichao; Liu, Fan; Ni, Hongbo; Yu, Zhiwen

2017-01-01

Background Sleep Apnea Syndrome (SAS) is a common sleep-related breathing disorder, which affects about 4-7% males and 2-4% females all around the world. Different approaches have been adopted to diagnose SAS and measure its severity, including the gold standard Polysomnography (PSG) in sleep study field as well as several alternative techniques such as single-channel ECG, pulse oximeter and so on. However, many shortcomings still limit their generalization in home environment. In this study, we aim to propose an efficient approach to automatically assess the severity of sleep apnea syndrome based on the ballistocardiogram (BCG) signal, which is non-intrusive and suitable for in home environment. Methods We develop an unobtrusive sleep monitoring system to capture the BCG signals, based on which we put forward a three-stage sleep apnea syndrome severity assessment framework, i.e., data preprocessing, sleep-related breathing events (SBEs) detection, and sleep apnea syndrome severity evaluation. First, in the data preprocessing stage, to overcome the limits of BCG signals (e.g., low precision and reliability), we utilize wavelet decomposition to obtain the outline information of heartbeats, and apply a RR correction algorithm to handle missing or spurious RR intervals. Afterwards, in the event detection stage, we propose an automatic sleep-related breathing event detection algorithm named Physio_ICSS based on the iterative cumulative sums of squares (i.e., the ICSS algorithm), which is originally used to detect structural breakpoints in a time series. In particular, to efficiently detect sleep-related breathing events in the obtained time series of RR intervals, the proposed algorithm not only explores the practical factors of sleep-related breathing events (e.g., the limit of lasting duration and possible occurrence sleep stages) but also overcomes the event segmentation issue (e.g., equal-length segmentation method might divide one sleep-related breathing event into different fragments and lead to incorrect results) of existing approaches. Finally, by fusing features extracted from multiple domains, we can identify sleep-related breathing events and assess the severity level of sleep apnea syndrome effectively. Conclusions Experimental results on 136 individuals of different sleep apnea syndrome severities validate the effectiveness of the proposed framework, with the accuracy of 94.12% (128/136). PMID:28445548

Eagle's Syndrome

PubMed Central

Pinheiro, Thaís Gonçalves; Soares, Vítor Yamashiro Rocha; Ferreira, Denise Bastos Lage; Raymundo, Igor Teixeira; Nascimento, Luiz Augusto; Oliveira, Carlos Augusto Costa Pires de

2013-01-01

Summary Introduction: Eagle's syndrome is characterized by cervicopharyngeal signs and symptoms associated with elongation of the styloid apophysis. This elongation may occur through ossification of the stylohyoid ligament, or through growth of the apophysis due to osteogenesis triggered by a factor such as trauma. Elongation of the styloid apophysis may give rise to intense facial pain, headache, dysphagia, otalgia, buzzing sensations, and trismus. Precise diagnosis of the syndrome is difficult, and it is generally confounded by other manifestations of cervicopharyngeal pain. Objective: To describe a case of Eagle's syndrome. Case Report: A 53-year-old man reported lateral pain in his neck that had been present for 30 years. Computed tomography (CT) of the neck showed elongation and ossification of the styloid processes of the temporal bone, which was compatible with Eagle's syndrome. Surgery was performed for bilateral resection of the stylohyoid ligament by using a transoral and endoscopic access route. The patient continued to present pain laterally in the neck, predominantly on his left side. CT was performed again, which showed elongation of the styloid processes. The patient then underwent lateral cervicotomy with resection of the stylohyoid process, which partially resolved his painful condition. Final Comments: Patients with Eagle's syndrome generally have a history of chronic pain. Appropriate knowledge of this disease is necessary for adequate treatment to be provided. The importance of diagnosing this uncommon and often unsuspected disease should be emphasized, given that correct clinical-surgical treatment is frequently delayed. The diagnosis of Eagle's syndrome is clinical and radiographic, and the definitive treatment in cases of difficult-to-control pain is surgical. PMID:25992033

Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling.

PubMed

Moon, Heejung; Song, Jieun; Shin, Jeong-Oh; Lee, Hankyu; Kim, Hong-Kyung; Eggenschwiller, Jonathan T; Bok, Jinwoong; Ko, Hyuk Wan

2014-06-10

Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder associated with multiple congenital defects in endocrine, cerebral, and skeletal systems that is caused by a missense mutation in the mitogen-activated protein kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK homologs are involved in flagellar formation and ciliogenesis, respectively. However, it is not clear whether this role of ICK is conserved in mammals and how a lack of functional ICK results in the characteristic phenotypes of human ECO syndrome. Here, we generated Ick knockout mice to elucidate the precise role of ICK in mammalian development and to examine the pathological mechanisms of ECO syndrome. Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes. In cultured cells, down-regulation of Ick or overexpression of kinase-dead or ECO syndrome mutant ICK resulted in an elongation of primary cilia and abnormal Sonic hedgehog (Shh) signaling. Wild-type ICK proteins were generally localized in the proximal region of cilia near the basal bodies, whereas kinase-dead ICK mutant proteins accumulated in the distal part of bulged ciliary tips. Consistent with these observations in cultured cells, Ick knockout mouse embryos displayed elongated cilia and reduced Shh signaling during limb digit patterning. Taken together, these results indicate that ICK plays a crucial role in controlling ciliary length and that ciliary defects caused by a lack of functional ICK leads to abnormal Shh signaling, resulting in congenital disorders such as ECO syndrome.

Genetics and aging; the Werner syndrome as a segmental progeroid syndrome.

PubMed

Martin, G M

1985-01-01

The maximum lifespan potential is a constitutional feature of speciation and must be subject to polygenic controls acting both in the domain of development and in the domain of the maintenance of macromolecular integrity. The enormous genetic heterogeneity that characterizes our own species, the complexities of numerous nature-nurture interactions, and the quantitative and qualitative variations of the senescent phenotype that are observed suggest that precise patterns of aging in each of us may be unique. Patterns of aging may also differ sharply among species (for example, semelparous vs. multiparous mammals). Some potential common denominators, however, allow one to identify progeroid syndromes in man that could lead to the elucidation of important pathways of gene action. (The suffix "-oid" means "like"; it does not mean identity.) Unimodal progeroid syndromes (eg., familial dementia of the Alzheimer type, an autosomal dominant) can help us understand the pathogenesis of a particular aspect of the senescent phenotype of man. Segmental progeroid syndromes (eg. the Werner syndrome, an autosomal recessive) may be relevant to multiple aspects of the senescent phenotype. Some results of research on the Werner syndrome may be interpreted as support for "peripheral" as opposed to "central" theories of aging; they are consistent with the view that gene action in the domain of development (adolescence, in this instance) can set the stage for patterns of aging in the adult; they point to the importance of mesenchymal cell populations in the pathogenesis of age-related disorders; finally, they underscore the role of chromosomal instability, especially in the pathogenesis of neoplasia.

A case series of pregnancy- and lactation-associated osteoporosis and a review of the literature

PubMed Central

Nakamura, Yukio; Kamimura, Mikio; Ikegami, Shota; Mukaiyama, Keijiro; Komatsu, Masatoshi; Uchiyama, Shigeharu; Kato, Hiroyuki

2015-01-01

The syndrome of pregnancy- and lactation-associated osteoporosis is a rare disorder whose precise etiology and treatment are largely unknown. We herein report two such cases occurring in the early postpartum period that led to multiple fragility compression fractures. Combination therapy of vitamin D and vitamin K enabled a marked gradual increase in bone mineral density. PMID:26379439

Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome in Japan, 2013–2014

PubMed Central

Shimada, Tomoe; Matsui, Tamano; Shimojima, Masayuki; Saijo, Masayuki; Oishi, Kazunori

2016-01-01

Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients. PMID:27776187

Epidemiological and Clinical Features of Severe Fever with Thrombocytopenia Syndrome in Japan, 2013-2014.

PubMed

Kato, Hirofumi; Yamagishi, Takuya; Shimada, Tomoe; Matsui, Tamano; Shimojima, Masayuki; Saijo, Masayuki; Oishi, Kazunori

2016-01-01

Although severe fever with thrombocytopenia syndrome (SFTS) was first reported from Japan in 2013, the precise clinical features and the risk factors for SFTS have not been fully investigated in Japan. Ninety-six cases of severe fever with thrombocytopenia syndrome (SFTS) were notified through the national surveillance system between April 2013 and September 2014 in Japan. All cases were from western Japan, and 82 cases (85%) had an onset between April and August. A retrospective observational study of the notified SFTS cases was conducted to identify the clinical features and laboratory findings during the same period. Of 96 notified cases, 49 (51%) were included in this study. Most case-patients were of advanced age (median age 78 years) and were retired or unemployed, or farmers. These case-patients had a history of outdoor activity within 2 weeks before the onset of illness. The median serum C-reactive protein concentration was slightly elevated at admission. Fungal infections such as invasive aspergilosis were found in 10% of these case-patients. Hemophagocytosis was observed in 15 of the 18 case-patients (83%) whose bone marrow samples were available. Fifteen cases were fatal, giving a case-fatality proportion of 31%. The proportion of neurological abnormalities and serum concentrations of lactate dehydrogenase and aspartate aminotransferase were significantly higher in the fatal cases than in the nonfatal cases during hospitalization. Appearance of neurological abnormality may be useful for predicting the prognosis in SFTS patients.

Epigenetics in focus: pathogenesis of myelodysplastic syndromes and the role of hypomethylating agents.

PubMed

Santini, Valeria; Melnick, Ari; Maciejewski, Jaroslaw P; Duprez, Estelle; Nervi, Clara; Cocco, Lucio; Ford, Kevin G; Mufti, Ghulam

2013-11-01

Dysregulation of cellular epigenetic machinery is considered a major pathogenetic determinant in many malignancies, including myelodysplastic syndromes (MDS). The importance of epigenetic dysfunction in MDS is reflected by the success of hypomethylating agents as standard of care for their treatment. Although these agents improve both survival and quality of life, knowledge gaps remain regarding the precise role of epigenetics in the pathogenesis of MDS and mechanisms by which hypomethylating agents exert their clinical effects. This article reviews the pathogenic role of epigenetic alterations in MDS, including the relationship between genetic and epigenetic abnormalities, and highlights emerging evidence that hypomethylating agents may reprogram the "methylome" while re-establishing hematopoiesis. Copyright © 2013. Published by Elsevier Ireland Ltd.

Exploring the association between metabolic syndrome components and polyneuropathy in an obese population

PubMed Central

Callaghan, Brian C.; Xia, Rong; Reynolds, Evan; Banerjee, Mousumi; Rothberg, Amy E.; Burant, Charles F.; Villegas-Umana, Emily; Pop-Busui, Rodica; Feldman, Eva L.

2016-01-01

Importance Past studies revealed an association between the metabolic syndrome and polyneuropathy, but the precise components that drive this association remain unclear. Objective We aimed to determine the prevalence of polyneuropathy stratified by glycemic status in well characterized obese and lean participants. We also investigated the association of specific metabolic syndrome components and polyneuropathy. Design We performed a cross-sectional, observational study in obese participants from a weight management program and lean controls from a research website. The prevalence of neuropathy, stratified by glycemic status, was determined, and a Mantel–Haenszel chi-square test was used to investigate for a trend. Logistic regression was used to model the primary polyneuropathy outcome as a function of the metabolic syndrome components after adjusting for demographic factors. Secondary outcomes included intraepidermal nerve fiber density and nerve conduction study parameters. Participants also completed quantitative sudomotor axon reflex testing, quantitative sensory testing, quality of life (Neuro-QOL), and pain (short form McGill Pain questionnaire) assessments. Setting Tertiary care, weight management program. Participants Obese patients were required to have a body mass index ≥ 35 kg/m^2 or ≥ 32 kg/m^2 if they had one or more comorbidity. Lean controls met no metabolic syndrome criteria (modified NCEP/ATPIII definition). Exposures Metabolic syndrome components (NCEP/ATPIII definition) including glycemic status (Expert Committee on the diagnosis and classification of diabetes mellitus definition). Main Outcome Toronto consensus definition of probable polyneuropathy. Results We enrolled 102 obese participants (44.1% normoglycemia, 30.4% pre-diabetes, and 25.5% diabetes) and 53 lean controls. The polyneuropathy prevalence was 3.8% in lean controls, 11.1% in the obese, normoglycemia group, 29.0%, in the obese, pre-diabetes group, and 34.6% in the obese, diabetes group (p<0.01 for trend). Age (OR=1.09, 95% CI 1.02–1.16), diabetes (OR=4.90, 95% CI 1.06–22.63), and waist circumference (OR=1.24, 95% CI 1.00–1.55) were significantly associated with neuropathy in multivariable models. Pre-diabetes (OR=3.82, 95% CI 0.95–15.41) approached, but did not reach, statistical significance. Conclusions and Relevance The polyneuropathy prevalence is high in an obese population even in those with normoglycemia. Diabetes, pre-diabetes, and obesity are the likely metabolic drivers of this neuropathy. PMID:27802497

Coexistence of ulcerative colitis and Sjögren's syndrome in a patient with Takayasu's arteritis and Hashimoto's thyroiditis.

PubMed

Park, Hyun Woo; Lee, Hyun Seok; Hwang, Sejin; Lee, Han Sol; Bae, Han-Ik; Yoon, Ghilsuk

2017-04-01

A 31-year-old woman with a 15-year history of Takayasu's arteritis (TA) and a 13-year history of Hashimoto's thyroiditis presented with hematochezia. She received a diagnosis of Sjögren's syndrome at 1 month before her visit to Kyungpook National University Medical Center. Her colonoscopic findings were compatible with a diagnosis of ulcerative colitis (UC). She was treated with oral mesalazine, and her hematochezia symptoms subsequently disappeared. The coexistence of UC and TA has been reported; however, reports on the coexistence of UC and Sjögren's syndrome, or of UC and Hashimoto's thyroiditis are rare. Although the precise etiologies of these diseases are unknown, their presence together suggests that they may have a common pathophysiologic background. Furthermore, in patients with autoimmune or vascular diseases, including TA, systemic manifestations should be assessed with consideration of inflammatory bowel diseases including UC in the presence of gastrointestinal symptoms such as diarrhea and hematochezia.

[On the benefits to keep using the asperger diagnosis].

PubMed

Delcommenne, M; Francolini, M; Bon, O L

The purpose of this paper is to examine the possible benefits to keep using the diagnosis of Asperger's syndrome. We first describe the evolution of this entity over time and within nomenclature bases such as the ICD- 10, the CFTMEA and the last versions of DSM. Then, we discuss more precisely the impact of the decision made in the DSM-5 to suppress the Asperger syndrome as a differentiated entity within the pervasive developmental disorders (PDD). This disorder chapter by the way also disappears and is replaced by Autism Spectrum Disorder (ASD). We present here three clinical cases encountered in an outpatient general child psychiatry clinic : 1 case was diagnosed as Asperger syndrome, 1 as infantile autism (early infantile autism) and 1 as another pervasive developmental disorder (psychotic disharmony). The objective was to expose the commonali ties and differences between these three entities. We conclude that keeping using the Asperger diagnosis is important for the clinical management of these clinical situations but also for the individual, his or her family and society at large.

TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome.

PubMed

Gray, Phillip N; Tsai, Pei; Chen, Daniel; Wu, Sitao; Hoo, Jayne; Mu, Wenbo; Li, Bing; Vuong, Huy; Lu, Hsiao-Mei; Batth, Navanjot; Willett, Sara; Uyeda, Lisa; Shah, Swati; Gau, Chia-Ling; Umali, Monalyn; Espenschied, Carin; Janicek, Mike; Brown, Sandra; Margileth, David; Dobrea, Lavinia; Wagman, Lawrence; Rana, Huma; Hall, Michael J; Ross, Theodora; Terdiman, Jonathan; Cullinane, Carey; Ries, Savita; Totten, Ellen; Elliott, Aaron M

2018-04-17

The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2 , MSH6 , MLH1 , PMS2 and EPCAM . Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases.

Emerging Antiepileptic Drugs for Severe Pediatric Epilepsies.

PubMed

Mudigoudar, Basanagoud; Weatherspoon, Sarah; Wheless, James W

2016-05-01

The medical management of the epilepsy syndromes of early childhood (eg, infantile spasms, Dravet syndrome, and Lennox-Gastaut syndrome) is challenging; and requires careful evaluation, classification, and treatment. Pharmacologic therapy continues to be the mainstay of management for these children, and as such it is important for the clinician to be familiar with the role of new antiepileptic drugs. This article reports the clinical trial data and personal experience in treating the severe epilepsies of childhood with the recently Food and Drug Administration-approved new antiepileptic drugs (vigabatrin, rufinamide, perampanel, and clobazam) and those in clinical trials (cannabidiol, stiripentol, and fenfluramine). Genetic research has also identified an increasing number of pediatric developmental and seizure disorders that are possibly treatable with targeted drug therapies, focused on correcting underlying neural dysfunction. We highlight recent genetic advances, and how they affect our treatment of some of the genetic epilepsies, and speculate on the use of targeted genetic treatment (precision medicine) in the future. Copyright © 2016 Elsevier Inc. All rights reserved.

TumorNext-Lynch-MMR: a comprehensive next generation sequencing assay for the detection of germline and somatic mutations in genes associated with mismatch repair deficiency and Lynch syndrome

PubMed Central

Gray, Phillip N.; Tsai, Pei; Chen, Daniel; Wu, Sitao; Hoo, Jayne; Mu, Wenbo; Li, Bing; Vuong, Huy; Lu, Hsiao-Mei; Batth, Navanjot; Willett, Sara; Uyeda, Lisa; Shah, Swati; Gau, Chia-Ling; Umali, Monalyn; Espenschied, Carin; Janicek, Mike; Brown, Sandra; Margileth, David; Dobrea, Lavinia; Wagman, Lawrence; Rana, Huma; Hall, Michael J.; Ross, Theodora; Terdiman, Jonathan; Cullinane, Carey; Ries, Savita; Totten, Ellen; Elliott, Aaron M.

2018-01-01

The current algorithm for Lynch syndrome diagnosis is highly complex with multiple steps which can result in an extended time to diagnosis while depleting precious tumor specimens. Here we describe the analytical validation of a custom probe-based NGS tumor panel, TumorNext-Lynch-MMR, which generates a comprehensive genetic profile of both germline and somatic mutations that can accelerate and streamline the time to diagnosis and preserve specimen. TumorNext-Lynch-MMR can detect single nucleotide variants, small insertions and deletions in 39 genes that are frequently mutated in Lynch syndrome and colorectal cancer. Moreover, the panel provides microsatellite instability status and detects loss of heterozygosity in the five Lynch genes; MSH2, MSH6, MLH1, PMS2 and EPCAM. Clinical cases are described that highlight the assays ability to differentiate between somatic and germline mutations, precisely classify variants and resolve discordant cases. PMID:29755653

Laparoscopic Removal of Streak Gonads in Turner Syndrome.

PubMed

Mandelberger, Adrienne; Mathews, Shyama; Andikyan, Vaagn; Chuang, Linus

To demonstrate the skills necessary for complete resection of bilateral streak gonads in Turner syndrome. Video case presentation with narration highlighting the key techniques used. The video was deemed exempt from formal review by our institutional review board. Turner syndrome is a form of gonadal dysgenesis that affects 1 in 2500 live births. Patients often have streak gonads and may present with primary amenorrhea or premature ovarian failure. Patients with a mosaic karyotype that includes a Y chromosome are at increased risk for gonadoblastoma and subsequent transformation into malignancy. Gonadectomy is recommended for these patients, typically at adolescence. Streak gonads can be difficult to identify, and tissue margins are often in close proximity to critical retroperitoneal structures. Resection can be technically challenging and requires a thorough understanding of retroperitoneal anatomy and precise dissection techniques to ensure complete removal. Laparoscopic approach to bilateral salpingo-oophorectomy of streak gonads. Retroperitoneal dissection and ureterolysis are performed, with the aid of the Ethicon Harmonic Ace, to ensure complete gonadectomy. Careful and complete resection of gonadal tissue in the hands of a skilled laparoscopic surgeon is key for effective cancer risk reduction surgery in Turner syndrome mosaics. Copyright © 2016 AAGL. Published by Elsevier Inc. All rights reserved.

Visuospatial declarative learning despite profound verbal declarative amnesia in Korsakoff's syndrome.

PubMed

Oudman, Erik; Postma, Albert; Nijboer, Tanja C W; Wijnia, Jan W; Van der Stigchel, Stefan

2017-03-20

Korsakoff's syndrome (KS) is a neuropsychiatric disorder characterised by severe amnesia. Although the presence of impairments in memory has long been acknowledged, there is a lack of knowledge about the precise characteristics of declarative memory capacities in order to implement memory rehabilitation. In this study, we investigated the extent to which patients diagnosed with KS have preserved declarative memory capacities in working memory, long-term memory encoding or long-term memory recall operations, and whether these capacities are most preserved for verbal or visuospatial content. The results of this study demonstrate that patients with KS have compromised declarative memory functioning on all memory indices. Performance was lowest for the encoding operation compared to the working memory and delayed recall operation. With respect to the content, visuospatial memory was relatively better preserved than verbal memory. All memory operations functioned suboptimally, although the most pronounced disturbance was found in verbal memory encoding. Based on the preserved declarative memory capacities in patients, visuospatial memory can form a more promising target for compensatory memory rehabilitation than verbal memory. It is therefore relevant to increase the number of spatial cues in memory rehabilitation for KS patients.

[Relations between hypertensive disorders in pregnancy and subsequent risk of early-term birth: a birth cohort study].

PubMed

Li, F Y; Yan, S Q; Huang, K; Mao, L J; Pan, W J; Ge, X; Han, Y; Hao, J H; Tao, F B

2017-12-10

Objective: To evaluate the relations between hypertensive disorders (HDP) in pregnancy and early-term birth. Methods: A total of 3 474 pregnant women were consecutively recruited. Demographic information was collected in early pregnancy. HDP was diagnosed in the first, second and third trimesters, respectively. On the basis of precise evaluation on gestation age, early-term birth was defined as gestational age of 37-38 weeks+6 days. Logistic regression models were conducted to examine the associations between HDP and early-term birth. Results: The current study included 3 260 pregnant women, with the rates of HDP, pregnancy-induced hypertension syndrome and pre-eclampsia as 6.0% ( n =194), 4.2% ( n =137) and 1.8% ( n =57), respectively. After controlling for potential confounders, no significant differences between pregnancy-induced hypertension syndrome and earlyterm birth ( OR =1.49, 95% CI : 0.94-2.36) were found. Pre-eclampsia appeared to have increased the risk of early-term birth ( OR =4.46, 95% CI : 2.09-9.54). Conclusion: Pre-eclampsia could significantly increase the risk of early-term birth. This finding suggested that early detection and intervention programs were helpful in reducing the risk of early-term birth.

Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.

PubMed

Haas, Joel T; Francque, Sven; Staels, Bart

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease-related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment.

Three-dimensional precise orientation of bilateral auricular trial prosthesis using a facebow for a young adult with Crouzon syndrome

PubMed Central

Rathee, Manu; Tamrakar, Amit Kumar; Kundu, Renu; Yunus, Nadeem

2014-01-01

Facial deformity can be debilitating, especially in the psychological and cosmetic aspects. Although surgical correction or replacement of deformed or missing parts is the ideal treatment, prosthetic replacement serves the purpose in case of surgical limitations. Prosthetic rehabilitation of a missing auricle is an acceptable option as it provides better control over the tortuous anatomical shape and shade of the missing portion. Improper spatial orientation of the prosthetic ear on the face can damage the results of even the most aesthetic prosthesis. This case report describes a simple and innovative method for precise spatial orientation of auricular trial prosthesis using a facebow and custom-made adjustable mechanical retention design using stainless steel wire. PMID:25096652

From shape to cells: mouse models reveal mechanisms altering palate development in Apert syndrome

PubMed Central

Martínez-Abadías, Neus; Holmes, Greg; Pankratz, Talia; Wang, Yingli; Zhou, Xueyan; Jabs, Ethylin Wang; Richtsmeier, Joan T.

2013-01-01

SUMMARY Apert syndrome is a congenital disorder characterized by severe skull malformations and caused by one of two missense mutations, S252W and P253R, on fibroblast growth factor receptor 2 (FGFR2). The molecular bases underlying differential Apert syndrome phenotypes are still poorly understood and it is unclear why cleft palate is more frequent in patients carrying the S252W mutation. Taking advantage of Apert syndrome mouse models, we performed a novel combination of morphometric, histological and immunohistochemical analyses to precisely quantify distinct palatal phenotypes in Fgfr2+/S252W and Fgfr2+/P253R mice. We localized regions of differentially altered FGF signaling and assessed local cell patterns to establish a baseline for understanding the differential effects of these two Fgfr2 mutations. Palatal suture scoring and comparative 3D shape analysis from high resolution μCT images of 120 newborn mouse skulls showed that Fgfr2+/S252W mice display relatively more severe palate dysmorphologies, with contracted and more separated palatal shelves, a greater tendency to fuse the maxillary-palatine sutures and aberrant development of the inter-premaxillary suture. These palatal defects are associated with suture-specific patterns of abnormal cellular proliferation, differentiation and apoptosis. The posterior region of the developing palate emerges as a potential target for therapeutic strategies in clinical management of cleft palate in Apert syndrome patients. PMID:23519026

Upper airway resistance syndrome.

PubMed

Montserrat, J M; Badia, J R

1999-03-01

This article reviews the clinical picture, diagnosis and management of the upper airway resistance syndrome (UARS). Presently, there is not enough data on key points like the frequency of UARS and the morbidity associated with this condition. Furthermore, the existence of LIARS as an independent sleep disorder and its relation with snoring and obstructive events is in debate. The diagnosis of UARS is still a controversial issue. The technical limitations of the classic approach to monitor airflow with thermistors and inductance plethysmography, as well as the lack of a precise definition of hypopnea, may have led to a misinterpretation of UARS as an independent diagnosis from the sleep apnea/hypopnea syndrome. The diagnosis of this syndrome can be missed using a conventional polysomnographic setting unless appropriate techniques are applied. The use of an esophageal balloon to monitor inspiratory effort is currently the gold standard. However, other sensitive methods such as the use of a pneumotachograph and, more recently, nasal cannula/pressure transducer systems or on-line monitoring of respiratory impedance with the forced oscillation technique may provide other interesting possibilities. Recognition and characterization of this subgroup of patients within sleep breathing disorders is important because they are symptomatic and may benefit from treatment. Management options to treat UARS comprise all those currently available for sleep apnea/hypopnea syndrome (SAHS). However, the subset of patients classically identified as LIARS that exhibit skeletal craneo-facial abnormalities might possibly obtain further benefit from maxillofacial surgery.

Classifying free-text triage chief complaints into syndromic categories with natural language processing.

PubMed

Chapman, Wendy W; Christensen, Lee M; Wagner, Michael M; Haug, Peter J; Ivanov, Oleg; Dowling, John N; Olszewski, Robert T

2005-01-01

Develop and evaluate a natural language processing application for classifying chief complaints into syndromic categories for syndromic surveillance. Much of the input data for artificial intelligence applications in the medical field are free-text patient medical records, including dictated medical reports and triage chief complaints. To be useful for automated systems, the free-text must be translated into encoded form. We implemented a biosurveillance detection system from Pennsylvania to monitor the 2002 Winter Olympic Games. Because input data was in free-text format, we used a natural language processing text classifier to automatically classify free-text triage chief complaints into syndromic categories used by the biosurveillance system. The classifier was trained on 4700 chief complaints from Pennsylvania. We evaluated the ability of the classifier to classify free-text chief complaints into syndromic categories with a test set of 800 chief complaints from Utah. The classifier produced the following areas under the ROC curve: Constitutional = 0.95; Gastrointestinal = 0.97; Hemorrhagic = 0.99; Neurological = 0.96; Rash = 1.0; Respiratory = 0.99; Other = 0.96. Using information stored in the system's semantic model, we extracted from the Respiratory classifications lower respiratory complaints and lower respiratory complaints with fever with a precision of 0.97 and 0.96, respectively. Results suggest that a trainable natural language processing text classifier can accurately extract data from free-text chief complaints for biosurveillance.

Worldwide Report, Arms Control.

DTIC Science & Technology

1985-04-09

is necessary to take care about the creation of the appropriate psychological and political atmosphere, to show a definite restraint. However as it...tension and pur- suing power politics. These are all signs of an old syndrome — the yearning for military superiority. Now that rough military-strategic...strategic aspects of these plans, the psychological calculation of the president and his aides was simple and very precise. It cannot be bad, surely

Relieving Painful 'Shin Splints'.

PubMed

Fick, Daniel S; Albright, John P; Murray, Boyd P

1992-12-01

In brief Shin splints, or more precisely, medial tibial stress syndrome (MTSS), are painful and troublesome. Despite treatment or activity modification, they often recur. Distinguishing MTSS, the most common running overuse injury, from other overuse injuries can help focus treatment, which starts conservatively. Recommending activity modification, ice massage, NSAIDs, and stretching is a good first step. Patients who don't respond to treatment may need additional diagnostic workup and more restrictive activity guidelines.

Congenital Myasthenic Syndromes or Inherited Disorders of Neuromuscular Transmission: Recent Discoveries and Open Questions

PubMed Central

Nicole, Sophie; Azuma, Yoshiteru; Bauché, Stéphanie; Eymard, Bruno; Lochmüller, Hanns; Slater, Clarke

2017-01-01

Congenital myasthenic syndromes (CMS) form a heterogeneous group of rare diseases characterized by fatigable muscle weakness. They are genetically-inherited and caused by defective synaptic transmission at the cholinergic neuromuscular junction (NMJ). The number of genes known to cause CMS when mutated is currently 30, and the relationship between fatigable muscle weakness and defective functions is quite well-understood for many of them. However, some of the most recent discoveries in individuals with CMS challenge our knowledge of the NMJ, where the basis of the pathology has mostly been investigated in animal models. Frontier forms between CMS and congenital myopathy, which have been genetically and clinically identified, underline the poorly understood interplay between the synaptic and extrasynaptic molecules in the neuromuscular system. In addition, precise electrophysiological and histopathological investigations of individuals with CMS suggest an important role of NMJ plasticity in the response to CMS pathogenesis. While efficient drug-based treatments are already available to improve neuromuscular transmission for most forms of CMS, others, as well as neurological and muscular comorbidities, remain resistant. Taken together, the available pathological data point to physiological issues which remain to be understood in order to achieve precision medicine with efficient therapeutics for all individuals suffering from CMS. PMID:29125502

A Precise Drunk Driving Detection Using Weighted Kernel Based on Electrocardiogram.

PubMed

Wu, Chung Kit; Tsang, Kim Fung; Chi, Hao Ran; Hung, Faan Hei

2016-05-09

Globally, 1.2 million people die and 50 million people are injured annually due to traffic accidents. These traffic accidents cost $500 billion dollars. Drunk drivers are found in 40% of the traffic crashes. Existing drunk driving detection (DDD) systems do not provide accurate detection and pre-warning concurrently. Electrocardiogram (ECG) is a proven biosignal that accurately and simultaneously reflects human's biological status. In this letter, a classifier for DDD based on ECG is investigated in an attempt to reduce traffic accidents caused by drunk drivers. At this point, it appears that there is no known research or literature found on ECG classifier for DDD. To identify drunk syndromes, the ECG signals from drunk drivers are studied and analyzed. As such, a precise ECG-based DDD (ECG-DDD) using a weighted kernel is developed. From the measurements, 10 key features of ECG signals were identified. To incorporate the important features, the feature vectors are weighted in the customization of kernel functions. Four commonly adopted kernel functions are studied. Results reveal that weighted feature vectors improve the accuracy by 11% compared to the computation using the prime kernel. Evaluation shows that ECG-DDD improved the accuracy by 8% to 18% compared to prevailing methods.

Nasal Involvement in Obstructive Sleep Apnea Syndrome

PubMed Central

Michels, Daniel de Sousa; Rodrigues, Amanda da Mota Silveira; Nakanishi, Márcio; Sampaio, André Luiz Lopes; Venosa, Alessandra Ramos

2014-01-01

Numerous studies have reported an association between nasal obstruction and obstructive sleep apnea syndrome (OSAS), but the precise nature of this relationship remains to be clarified. This paper aimed to summarize data and theories on the role of the nose in the pathophysiology of sleep apnea as well as to discuss the benefits of surgical and medical nasal treatments. A number of pathophysiological mechanisms can potentially explain the role of nasal pathology in OSAS. These include the Starling resistor model, the unstable oral airway, the nasal ventilatory reflex, and the role of nitric oxide (NO). Pharmacological treatment presents some beneficial effects on the frequency of respiratory events and sleep architecture. Nonetheless, objective data assessing snoring and daytime sleepiness are still necessary. Nasal surgery can improve the quality of life and snoring in a select group of patients with mild OSAS and septal deviation but is not an effective treatment for OSA as such. Despite the conflicting results in the literature, it is important that patients who are not perfectly adapted to CPAP are evaluated in detail, in order to identify whether there are obstructive factors that could be surgically corrected. PMID:25548569

Autopsies of sudden infant death syndrome--classification and epidemiology.

PubMed

Hatton, F; Bouvier-Colle, M H; Barois, A; Imbert, M C; Leroyer, A; Bouvier, S; Jougla, E

1995-12-01

An enquiry into sudden infant death syndrome (SIDS) in 1987 furnished us with detailed epidemiological data for 281 cases that underwent a thorough post-mortem examination. This analysis uses these data to evaluate the role the autopsy plays in explaining sudden death. The cases were classified into three diagnostic groups: explained causes of death (group 1), unexplained deaths with anomalies (group 2), and no anomaly (group 3). These 281 cases show the three essential features that characterize SIDS: over-representation of males, increased deaths during the second and third months of life, and increased deaths during winter. The autopsy examination revealed that many of these deaths had a medical explanation. Almost half were assigned to group 1. At the time of autopsy, no precise pathology could be diagnosed for 147 deaths; of these, 140 showed histological anomalies. There were only seven sudden deaths for which no abnormal sign was evident at the autopsy. These results are compared with those of similar studies and discussed in connection with three factors: the initial selection of cases, the nature and degree of the investigations, and the possible interpretations of the symptoms uncovered.

DNAemia detection by multiplex PCR and biomarkers for infection in systemic inflammatory response syndrome patients.

PubMed

Fitting, Catherine; Parlato, Marianna; Adib-Conquy, Minou; Memain, Nathalie; Philippart, François; Misset, Benoît; Monchi, Mehran; Cavaillon, Jean-Marc; Adrie, Christophe

2012-01-01

Fast and reliable assays to precisely define the nature of the infectious agents causing sepsis are eagerly anticipated. New molecular biology techniques are now available to define the presence of bacterial or fungal DNA within the bloodstream of sepsis patients. We have used a new technique (VYOO®) that allows the enrichment of microbial DNA before a multiplex polymerase chain reaction (PCR) for pathogen detection provided by SIRS-Lab (Jena, Germany). We analyzed 72 sepsis patients and 14 non-infectious systemic inflammatory response syndrome (SIRS) patients. Among the sepsis patients, 20 had a positive blood culture and 35 had a positive microbiology in other biological samples. Of these, 51.4% were positive using the VYOO® test. Among the sepsis patients with a negative microbiology and the non-infectious SIRS, 29.4% and 14.2% were positive with the VYOO® test, respectively. The concordance in bacterial identification between microbiology and the VYOO® test was 46.2%. This study demonstrates that these new technologies offer great hopes, but improvements are still needed.

[Specificity hypothesis of a theory of mind deficit in early childhood autism].

PubMed

Kissgen, R; Schleiffer, R

2002-02-01

In order to test the hypothesis that a theory of mind deficit is specific for autism, the present study presents the first replication of the Sally-Anne test (Baron-Cohen, Leslie & Frith, 1985) in the German-speaking countries. The Sally-Anne test was administered to 16 autistic, 24 probands with Down's syndrome and 20 normal preschool prosands. The intelligence of the autistic group and that with Down's syndrome was measured by the CPM/SPM. In addition, the ADI-R was used with the principal caregivers of the autistic and Down's syndrome subjects. With regard to the clinical diagnosis, theory of mind deficit turned out to be not specific for autism. Six of 16 (37.5%) autistic subjects passed the theory of mind tasks. Thus performance in the autistic group surpassed that of both control groups. Out of 16 autistic subjects, autism could be confirmed in only 8 on the basis of the ADI-R diagnostic criteria, only one of whom showed a theory of mind. The autistic individuals with a theory of mind differed significantly in their mean IQ from those without this ability. Spectrum and specificity of a theory of mind deficit in autism remain controversial. For further research it seems important to administer the ADI-R during the diagnostic process. The findings suggest that the clinical diagnosis of autism is not precise enough to distinguish between autism and nonautistic mental handicap.

A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long QT Syndrome

PubMed Central

Limpitikul, Worawan B.; Dick, Ivy E.; Tester, David J.; Boczek, Nicole J.; Limphong, Pattraranee; Yang, Wanjun; Choi, Myoung Hyun; Babich, Jennifer; DiSilvestre, Deborah; Kanter, Ronald J.; Tomaselli, Gordon F.; Ackerman, Michael J.; Yue, David T.

2017-01-01

Rationale Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long QT syndrome (LQTS) with mutations involving either CALM1, CALM2, or CALM3. The underlying basis of this form of LQTS is a disruption of Ca2+/CaM-dependent inactivation (CDI) of L-type Ca2+ channels (LTCCs). Objective To gain insight into the mechanistic underpinnings of calmodulinopathies and devise new therapeutic strategies for the treatment of this form of LQTS. Methods and Results We generated and characterized the functional properties of iPSC-derived cardiomyocytes (iPSC-CMs) from a patient with D130G-CALM2-mediated LQTS, thus creating a platform with which to devise and test novel therapeutic strategies. The patient-derived iPSC-CMs display (1) significantly prolonged action potentials (APs), (2) disrupted Ca2+ cycling properties, and (3) diminished CDI of LTCCs. Next, taking advantage of the fact that calmodulinopathy patients harbor a mutation in only one of six redundant CaM-encoding alleles, we devised a strategy using CRISPR interference (CRISPRi) to selectively suppress the mutant gene while sparing the wild-type counterparts. Indeed, suppression of CALM2 expression produced a functional rescue in iPSC-CMs with D130G-CALM2, as shown by the normalization of AP duration and CDI following treatment. Moreover, CRISPRi can be designed to achieve selective knockdown of any of the three CALM genes, making it a generalizable therapeutic strategy for any calmodulinopathy. Conclusions Overall, this therapeutic strategy holds great promise for calmodulinopathy patients as it represents a generalizable intervention capable of specifically altering CaM expression and potentially attenuating LQTS-triggered cardiac events, thus initiating a path towards precision medicine. PMID:27765793

Chronic shin splints. Classification and management of medial tibial stress syndrome.

PubMed

Detmer, D E

1986-01-01

A clinical classification and treatment programme has been developed for chronic medial tibial stress syndrome. Medial tibial stress syndrome has been reported to be either tibial stress fracture or microfracture, tibial periostitis, or distal deep posterior chronic compartment syndrome. Three chronic types exist and may coexist: Type I (tibial microfracture, bone stress reaction or cortical fracture); type II (periostalgia from chronic avulsion of the periosteum at the periosteal-fascial junction); and type III (chronic compartment syndrome syndrome). Type I disease is treated nonoperatively. Operations for resistant types II and III medial tibial stress syndrome were performed in 41 patients. Bilaterality was common (type II, 50% type III, 88%). Seven had coexistent type II/III; one had type I/II. Preoperative symptoms averaged 24 months in type II, 6 months in type III, and 33 months in types II/III. Mean age was 22 years (15 to 51). Resting compartment pressures were normal in type II (mean 12 mm Hg) and elevated in type III and type II/III (mean 23 mm Hg). Type II and type II/III patients received fasciotomy plus periosteal cauterisation. Type III patients had fasciotomy only. All procedures were performed on an outpatient basis using local anaesthesia. Follow up was complete and averaged 6 months (2 to 14 months). Improved performance was as follows: type II, 93%, type III, 100%; type II/III, 86%. Complete cures were as follows: type II, 78%; type III, 75%; and type II/III, 57%. This experience suggests that with precise diagnosis and treatment involving minimal risk and cost the athlete has a reasonable chance of return to full activity.

Neuroanatomy and neuropathology associated with Korsakoff's syndrome.

PubMed

Kril, Jillian J; Harper, Clive G

2012-06-01

Although the neuropathology of Korsakoff's syndrome (KS) was first described well over a century ago and the characteristic brain pathology does not pose a diagnostic challenge to pathologists, there is still controversy over the neuroanatomical substrate of the distinctive memory impairment in these patients. Cohort studies of KS suggest a central role for the mammillary bodies and mediodorsal thalamus, and quantitative studies suggest additional damage to the anterior thalamus is required. Rare cases of KS caused by pathologies other than those of nutritional origin provide support for the role of the anterior thalamus and mammillary bodies. Taken together the evidence to date shows that damage to the thalamus and hypothalamus is required, in particular the anterior thalamic nucleus and the medial mammillary nucleus of the hypothalamus. As these nuclei form part of wider memory circuits, damage to the inter-connecting white matter tracts can also result in a similar deficit as direct damage to the nuclei. Although these nuclei and their connections appear to be the primary site of damage, input from other brain regions within the circuits, such as the frontal cortex and hippocampus, or more distant regions, including the cerebellum and amygdala, may have a modulatory role on memory function. Further studies to confirm the precise site(s) and extend of brain damage necessary for the memory impairment of KS are required.

Lessons from the atomic bomb about secondary MDS.

PubMed

Hata, Tomoko; Imanishi, Daisuke; Miyazaki, Yasushi

2014-12-01

Myelodysplastic syndromes (MDSs) is a hematological neoplasm defined by ineffective hematopoiesis, dysplasia of hematopoietic cells, and risk of progression to acute leukemia. MDS occurs as de novo or secondary, and chemoradiotherapy for cancers is thought to increase the risk of MDS among patients. Recently, an epidemiological study for MDS among A-bomb survivors was performed, and it clearly demonstrated that the exposure to external radiation significantly increased the risk of MDS. Precise epidemiological data among survivors have revealed important clinical factors related to the risk of leukemias. In this review, by comparing data for secondary MDS and leukemia/MDS among survivors, several factors which would affect the risk of MDS, especially secondary MDS, are discussed.

[The elbow joint - a diagnostic challenge : anatomy, biomechanics, and pathology].

PubMed

Schueller-Weidekamm, C; Kainberger, F

2008-12-01

The elbow is one of the most commonly injured joints in sports activities. In particular, weight lifters, golfers, tennis players, and pitchers are affected. Injuries in sports involving overhead throwing are commonly based on the pathophysiologic model of valgus extension overload syndrome. The injuries are commonly complex and demand a good knowledge of the symptoms, the exact anatomy, and the biomechanics to arrive at a precise radiologic diagnosis. The characteristic patterns of injury that occur in specific sports activities are related to a combination of increased varus or valgus and extension or flexion overload that results in tensile forces and/or compression and shear stress. Acute symptoms are frequently based on chronic degeneration of the tendons and ligamentous structures due to repetitive microtrauma from overuse syndrome.

De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy.

PubMed

Ambrosino, Paolo; Soldovieri, Maria Virginia; Bast, Thomas; Turnpenny, Peter D; Uhrig, Sabine; Biskup, Saskia; Döcker, Miriam; Fleck, Thilo; Mosca, Ilaria; Manocchio, Laura; Iraci, Nunzio; Taglialatela, Maurizio; Lemke, Johannes R

2018-05-08

Variants in several potassium channel genes have been found in developmental and epileptic encephalopathies (DEE). We report two females with de novo variants in KCNT2 with West syndrome followed by Lennox-Gastaut syndrome or with DEE with migrating focal seizures. After in vitro analysis suggested quinidine-responsive gain-of-function effects, we treated one of the girls with quinidine add-on therapy and achieved marked clinical improvements. This suggests that the new spectrum of KCNT2-related disorders do not only share similar phenotypic and in vitro functional and pharmacological features with previously known KCNT1-related disorders but also represents a further example for possible precision medicine approaches. This article is protected by copyright. All rights reserved. © 2018 American Neurological Association.

[Metabolic safety of antidepressant medicines].

PubMed

Łężak, Wojciech; Mokros, Łukasz; Karbownik, Michał Seweryn; Witusik, Andrzej; Kosmalski, Marcin; Kowalczyk, Edward; Pietras, Tadeusz

2017-05-23

Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

Micro-instillation of fluorescein with an inoculation loop for ocular surface staining in dry eye syndrome.

PubMed

Courrier, Emilie; Renault, Didier; Kaspi, Mathilde; Marcon, Agathe; Lambert, Victor; Garcin, Thibaud; Chiambaretta, Frederic; Garhofer, Gerhard; Thuret, Gilles; Gain, Philippe

2018-03-01

To describe and validate the micro-instillation of fluorescein on the ocular surface by a disposable calibrated inoculation loop to improve corneal and conjunctival staining quality. Accuracy and precision of the volume of 0.5% sodium fluorescein collected by a single use 1 μl-calibrated inoculation loop were measured using a precision balance. Twenty patients (40 eyes) suffering from dry eye syndrome were enrolled in a prospective interventional nonrandomized study. Fluorescein was instilled with the loop, and slit-lamp images were taken within 30 seconds using cobalt blue light with and without a yellow barrier filter. For comparison, after a washout period, the same images were retaken after instillation of one drop of fluorescein from a single-dose unit. The main outcome measure was the staining quality assessed by three experts, blind to the instillation method. Patient discomfort (tolerance, by a questionnaire) was also compared. The mean volume collected by the loop was 1.18 ± 0.12 μl, compared with 33.70 ± 6.10 μl using the single-dose unit. The loop avoided excess dye responsible for unpleasant tearing, masking of lesions and rapid diffusion into the stroma. Micro-instillation greatly improved image quality without losing information. The yellow filter further improved image contrast. Tolerance was excellent. The 1 μl-calibrated inoculation loop is a safe, convenient, inexpensive, disposable, sterile, well-tolerated tool for reproducible micro-instillation of commercial fluorescein. By greatly improving staining quality, it will help standardize assessment of dry eye severity. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

Tensor Factorization for Precision Medicine in Heart Failure with Preserved Ejection Fraction

PubMed Central

Luo, Yuan; Ahmad, Faraz S.; Shah, Sanjiv J.

2017-01-01

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome that may benefit from improved subtyping in order to better characterize its pathophysiology and to develop novel targeted therapies. The United States Precision Medicine Initiative comes amid the rapid growth in quantity and modality of clinical data for HFpEF patients ranging from deep phenotypic to trans-omic data. Tensor factorization, a form of machine learning, allows for the integration of multiple data modalities to derive clinically relevant HFpEF subtypes that may have significant differences in underlying pathophysiology and differential response to therapies. Tensor factorization also allows for better interpretability by supporting dimensionality reduction and identifying latent groups of data for meaningful summarization of both features and disease outcomes. In this narrative review, we analyze the modest literature on the application of tensor factorization to related biomedical fields including genotyping and phenotyping. Based on the cited work including work of our own, we suggest multiple tensor factorization formulations capable of integrating the deep phenotypic and trans-omic modalities of data for HFpEF, or accounting for interactions between genetic variants at different -omic hierarchies. We encourage extensive experimental studies to tackle challenges in applying tensor factorization for precision medicine in HFpEF, including effectively incorporating existing medical knowledge, properly accounting for uncertainty, and efficiently enforcing sparsity for better interpretability. PMID:28116551

Design, development and validation of a new laryngo-pharyngeal endoscopic esthesiometer and range-finder based on the assessment of air-pulse variability determinants.

PubMed

Giraldo-Cadavid, Luis F; Agudelo-Otalora, Luis Mauricio; Burguete, Javier; Arbulu, Mario; Moscoso, William Daniel; Martínez, Fabio; Ortiz, Andrés Felipe; Diaz, Juan; Pantoja, Jaime A; Rueda-Arango, Andrés Felipe; Fernández, Secundino

2016-05-10

Laryngo-pharyngeal mechano-sensitivity (LPMS) is involved in dysphagia, sleep apnea, stroke, irritable larynx syndrome and cough hypersensitivity syndrome among other disorders. These conditions are associated with a wide range of airway reflex abnormalities. However, the current device for exploring LPMS is limited because it assesses only the laryngeal adductor reflex during fiber-optic endoscopic evaluations of swallowing and requires a high degree of expertise to obtain reliable results, introducing intrinsic expert variability and subjectivity. We designed, developed and validated a new air-pulse laryngo-pharyngeal endoscopic esthesiometer with a built-in laser range-finder (LPEER) based on the evaluation and control of air-pulse variability determinants and on intrinsic observer variability and subjectivity determinants of the distance, angle and site of stimulus impact. The LPEER was designed to be capable of delivering precise and accurate stimuli with a wide range of intensities that can explore most laryngo-pharyngeal reflexes. We initially explored the potential factors affecting the reliability of LPMS tests and included these factors in a multiple linear regression model. The following factors significantly affected the precision and accuracy of the test (P < 0.001): the tube conducting the air-pulses, the supply pressure of the system, the duration of the air-pulses, and the distance and angle between the end of the tube conducting the air-pulses and the site of impact. To control all of these factors, an LPEER consisting of an air-pulse generator and an endoscopic laser range-finder was designed and manufactured. We assessed the precision and accuracy of the LPEER's stimulus and range-finder according to the coefficient of variation (CV) and by looking at the differences between the measured properties and the desired values, and we performed a pilot validation on ten human subjects. The air-pulses and range-finder exhibited good precision and accuracy (CV < 0.06), with differences between the desired and measured properties at <3 % and a range-finder measurement error of <1 mm. The tests in patients demonstrated obtainable and reproducible thresholds for the laryngeal adductor, cough and gag reflexes. The new LPEER was capable of delivering precise and accurate stimuli for exploring laryngo-pharyngeal reflexes.

Eliminating barriers to personalized medicine

PubMed Central

2014-01-01

With the emergence of high-throughput discovery platforms, robust preclinical small-animal models, and efficient clinical trial pipelines, it is becoming possible to envision a time when the treatment of human neurologic diseases will become personalized. The emergence of precision medicine will require the identification of subgroups of patients most likely to respond to specific biologically based therapies. This stratification only becomes possible when the determinants that contribute to disease heterogeneity become more fully elucidated. This review discusses the defining factors that underlie disease heterogeneity relevant to the potential for individualized brain tumor (optic pathway glioma) treatments arising in the common single-gene cancer predisposition syndrome, neurofibromatosis type 1 (NF1). In this regard, NF1 is posited as a model genetic condition to establish a workable paradigm for actualizing precision therapeutics for other neurologic disorders. PMID:24975854

Three-dimensional precise orientation of bilateral auricular trial prosthesis using a facebow for a young adult with Crouzon syndrome.

PubMed

Rathee, Manu; Tamrakar, Amit Kumar; Kundu, Renu; Yunus, Nadeem

2014-08-05

Facial deformity can be debilitating, especially in the psychological and cosmetic aspects. Although surgical correction or replacement of deformed or missing parts is the ideal treatment, prosthetic replacement serves the purpose in case of surgical limitations. Prosthetic rehabilitation of a missing auricle is an acceptable option as it provides better control over the tortuous anatomical shape and shade of the missing portion. Improper spatial orientation of the prosthetic ear on the face can damage the results of even the most aesthetic prosthesis. This case report describes a simple and innovative method for precise spatial orientation of auricular trial prosthesis using a facebow and custom-made adjustable mechanical retention design using stainless steel wire. 2014 BMJ Publishing Group Ltd.

IMPACT OF FOOD ENRICHED WITH DIETARY FIBER ON PATIENTS WITH CONSTIPATION PREDOMINANT IRRITABLE BOWEL SYNDROME.

PubMed

Sulaberidze, G; Okujava, M; Liluashvili, K; Tughushi, M; Abramashvili, M

2017-03-01

The causes of motility disorder of gastrointestinal tract and in particular Irritable Bowel Syndrome IBS are multifold, leading to complexity of treatment and requirement of more precise investigation of different pharmacological and non-pharmacological approaches. The aim of the study was investigation and comparison of the dietary fiber intake among women with constipation-predominant irritable bowel syndrome (IBS-C) and without, improvement of the dietary fiber intake using interventions with less rough changes of food related behavior and study of its effects on the bowel function, general wellbeing and compliance of patients. In total 100 healthy women, without any clinical signs of gastrointestinal disorders and 98 women who met Rome III criteria of IBS-C were enrolled in the dietary fiber intake assessment survey. The dietary habits of all participants, as well as bowel function, digestive feelings and general wellbeing of patients at baseline, on the 7th and 14th day of dietary intervention was assessed by the means of adopted questionnaires. The dietary supplementation was provided during the breakfast with fiber enriched food - bread and muesli. Research data reviled significantly lower daily intake of dietary fiber among patients with IBS-C compared with healthy group. The main source of dietary fiber in IBS-C group was bread and cereals, therefore introduction of dietary fiber rich bread and muesli in the breakfast didn't affect diet-related habits and determined high compliance of patients. Two week long intervention significantly improved the bowel function and irritation related complains, the feeling of general wellbeing was considerably better on the endpoint as well.

A Chromosome 7 Pericentric Inversion Defined at Single-Nucleotide Resolution Using Diagnostic Whole Genome Sequencing in a Patient with Hand-Foot-Genital Syndrome.

PubMed

Watson, Christopher M; Crinnion, Laura A; Harrison, Sally M; Lascelles, Carolina; Antanaviciute, Agne; Carr, Ian M; Bonthron, David T; Sheridan, Eamonn

2016-01-01

Next generation sequencing methodologies are facilitating the rapid characterisation of novel structural variants at nucleotide resolution. These approaches are particularly applicable to variants initially identified using alternative molecular methods. We report a child born with bilateral postaxial syndactyly of the feet and bilateral fifth finger clinodactyly. This was presumed to be an autosomal recessive syndrome, due to the family history of consanguinity. Karyotype analysis revealed a homozygous pericentric inversion of chromosome 7 (46,XX,inv(7)(p15q21)x2) which was confirmed to be heterozygous in both unaffected parents. Since the resolution of the karyotype was insufficient to identify any putatively causative gene, we undertook medium-coverage whole genome sequencing using paired-end reads, in order to elucidate the molecular breakpoints. In a two-step analysis, we first narrowed down the region by identifying discordant read-pairs, and then determined the precise molecular breakpoint by analysing the mapping locations of "soft-clipped" breakpoint-spanning reads. PCR and Sanger sequencing confirmed the identified breakpoints, both of which were located in intergenic regions. Significantly, the 7p15 breakpoint was located 523 kb upstream of HOXA13, the locus for hand-foot-genital syndrome. By inference from studies of HOXA locus control in the mouse, we suggest that the inversion has delocalised a HOXA13 enhancer to produce the phenotype observed in our patient. This study demonstrates how modern genetic diagnostic approach can characterise structural variants at nucleotide resolution and provide potential insights into functional regulation.

Temperament as a unifying basis for personality and psychopathology.

PubMed

Clark, Lee Anna

2005-11-01

Personality and psychopathology long have been viewed as related domains, but the precise nature of their relations remains unclear. Through most of the 20th century, they were studied as separate fields; within psychopathology, clinical syndromes were separated from personality disorders in 1980. This division led to the revelation of substantial overlap among disorders both within and across axes and to the joint study of normal and abnormal personality. The author reviews these literatures and proposes an integrative framework to explain personality-psychopathology relations: Three broad, innate temperament dimensions--negative affectivity, positive affectivity, and disinhibition--differentiate through both biologically and environmentally based developmental processes into a hierarchical personality trait structure and, at their extremes, are risk factors (diatheses) for psychopathology, especially given adverse life experiences (stress). Copyright (c) 2005 APA, all rights reserved.

Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic beta-cells.

PubMed

Hatanaka, Masayuki; Tanabe, Katsuya; Yanai, Akie; Ohta, Yasuharu; Kondo, Manabu; Akiyama, Masaru; Shinoda, Koh; Oka, Yoshitomo; Tanizawa, Yukio

2011-04-01

Wolfram syndrome is an autosomal recessive disorder characterized by juvenile-onset insulin-dependent diabetes mellitus and optic atrophy. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER) resident transmembrane protein. The Wfs1-null mouse exhibits progressive insulin deficiency causing diabetes. Previous work suggested that the function of the WFS1 protein is connected to unfolded protein response and to intracellular Ca(2+) homeostasis. However, its precise molecular function in pancreatic β-cells remains elusive. In our present study, immunofluorescent and electron-microscopic analyses revealed that WFS1 localizes not only to ER but also to secretory granules in pancreatic β-cells. Intragranular acidification was assessed by measuring intracellular fluorescence intensity raised by the acidotrophic agent, 3-[2,4-dinitroanilino]-3'-amino-N-methyldipropyramine. Compared with wild-type β-cells, there was a 32% reduction in the intensity in WFS1-deficient β-cells, indicating the impairment of granular acidification. This phenotype may, at least partly, account for the evidence that Wfs1-null islets have impaired proinsulin processing, resulting in an increased circulating proinsulin level. Morphometric analysis using electron microscopy evidenced that the density of secretory granules attached to the plasma membrane was significantly reduced in Wfs1-null β-cells relative to that in wild-type β-cells. This may be relevant to the recent finding that granular acidification is required for the priming of secretory granules preceding exocytosis and may partly explain the fact that glucose-induced insulin secretion is profoundly impaired in young prediabetic Wfs1-null mice. These results thus provide new insights into the molecular mechanisms of β-cell dysfunction in patients with Wolfram syndrome.

"Scleroderma linearis: hemiatrophia faciei progressiva (Parry-Romberg syndrom) without any changes in CNS and linear scleroderma "en coup de sabre" with CNS tumor

PubMed Central

Bergler-Czop, Beata; Lis-Święty, Anna; Brzezińska-Wcisło, Ligia

2009-01-01

Background Hemifacial atrophy (Parry-Romberg syndrome) is a relatively rare disease. The etiology of the disease is not clear. Some authors postulate its relation with limited scleroderma linearis. Linear scleroderma "en coup de sabre" is characterized by clinical presence of most commonly one-sided linear syndrome. In a number of patients, neurological affection is the medium of the disease. The treatment of both scleroderma varieties is similar to the treatment of limited systemic sclerosis. Case presentation We present two cases of a disease: a case of a 49-year-old woman with a typical image of hemifacial atrophy, without any changes of the nervous system and a case of a 33-year-old patient with an "en coup de sabre" scleroderma and with CNS tumor. Conclusion We described typical cases of a rare diseases, hemifacial atrophy and "en coup de sabre" scleroderma. In the patient diagnosed with Parry-Romberg syndrome, with Borrelia burgdoferi infection and with minor neurological symptoms, despite a four-year case history, there was a lack of proper diagnosis and treatment. In the second patient only skin changes without any neurological symptoms could be observed and only a precise neurological diagnosis revealed the presence of CNS tumor. PMID:19635150

Year in review 2005: Critical Care – nephrology

PubMed Central

Ricci, Zaccaria; Ronco, Claudio

2006-01-01

We summarize original research in the field of critical care nephrology accepted or published in 2005 in Critical Care and, when considered relevant or directly linked to this research, in other journals. The articles have been grouped into four categories to facilitate a rapid overview. First, physiopathology, epidemiology and prognosis of acute renal failure (ARF): an extensive review and some observational studies have been performed with the aim of describing aspects of ARF physiopathology, precise epidemiology and long-term outcomes. Second, several authors have performed clinical trials utilizing a potential nephro-protective drug, fenoldopam, with different results. Third, the issue of continuous renal replacement therapies dose has been addressed in a small prospective study and a large observational trial. And fourth, alternative indications to extracorporeal treatment of ARF and systemic inflammatory response syndrome have been explored by three original clinical studies. PMID:16919174

High-Resolution Analysis of Coronavirus Gene Expression by RNA Sequencing and Ribosome Profiling

PubMed Central

Jones, Joshua D.; Chung, Betty Y.-W.; Siddell, Stuart G.; Brierley, Ian

2016-01-01

Members of the family Coronaviridae have the largest genomes of all RNA viruses, typically in the region of 30 kilobases. Several coronaviruses, such as Severe acute respiratory syndrome-related coronavirus (SARS-CoV) and Middle East respiratory syndrome-related coronavirus (MERS-CoV), are of medical importance, with high mortality rates and, in the case of SARS-CoV, significant pandemic potential. Other coronaviruses, such as Porcine epidemic diarrhea virus and Avian coronavirus, are important livestock pathogens. Ribosome profiling is a technique which exploits the capacity of the translating ribosome to protect around 30 nucleotides of mRNA from ribonuclease digestion. Ribosome-protected mRNA fragments are purified, subjected to deep sequencing and mapped back to the transcriptome to give a global “snap-shot” of translation. Parallel RNA sequencing allows normalization by transcript abundance. Here we apply ribosome profiling to cells infected with Murine coronavirus, mouse hepatitis virus, strain A59 (MHV-A59), a model coronavirus in the same genus as SARS-CoV and MERS-CoV. The data obtained allowed us to study the kinetics of virus transcription and translation with exquisite precision. We studied the timecourse of positive and negative-sense genomic and subgenomic viral RNA production and the relative translation efficiencies of the different virus ORFs. Virus mRNAs were not found to be translated more efficiently than host mRNAs; rather, virus translation dominates host translation at later time points due to high levels of virus transcripts. Triplet phasing of the profiling data allowed precise determination of translated reading frames and revealed several translated short open reading frames upstream of, or embedded within, known virus protein-coding regions. Ribosome pause sites were identified in the virus replicase polyprotein pp1a ORF and investigated experimentally. Contrary to expectations, ribosomes were not found to pause at the ribosomal frameshift site. To our knowledge this is the first application of ribosome profiling to an RNA virus. PMID:26919232

Rumination syndrome: when the lower oesophageal sphincter rises.

PubMed

Gourcerol, Guillaume; Dechelotte, Pierre; Ducrotte, Philippe; Leroi, Anne Marie

2011-07-01

Rumination syndrome is an uncommon condition characterised by the self-induced regurgitation from the stomach to the mouth of recently ingested meal that is chewed and reswallowed. Rumination is caused by a voluntary rise in intra-abdominal and intra-gastric pressure leading to the reflux of the gastric content into the oesophagus. However, the precise mechanisms preventing reflux at the gastro-oesophageal junction during the rise in intra-gastric pressure remains unknown. In 5 patients, rumination episodes were monitored using combined multiple intra-luminal impedance monitoring, high resolution manometry, and video-fluoroscopic recording. We showed that the gastro-oesophageal junction moved from the abdominal cavity into the thorax creating a "pseudo-hernia". This occurred at a range of 1.4 ± 0.3 s before the rise in intra-oesophageal pressure and the gastro-oesophageal reflux. This displacement of the gastro-oesophageal junction into thorax, rather than a lower oesophageal sphincter opening, explains the mechanism of voluntary regurgitations occurring during rumination syndrome. Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Pathogenesis and morbidity of autoantibody syndromes in Waldenstrom's macroglobulinemia.

PubMed

Stone, Marvin J

2011-02-01

A number of autoantibody syndromes have been identified that are mediated by monoclonal macroglobulins. Chronic cold agglutinin disease (CAD), mixed cryoglobulinemia (MC), and various polyneuropathies produce symptoms and signs such as cold sensitivity and sensorimotor neuropathies that bring the patients to attention ("the patients tell you"). Many of these patients would be classified as having monoclonal gammopathy of undetermined significance (MGUS) were it not for the consequences of antigen-antibody interaction. Other patients with autoantibody syndromes have overt Waldenström's macroglobulinemia (WM). These individuals present at an earlier stage than WM patients who do not have evident antibody activity. Thus the presence of autoreactive antibodies influences clinical presentation and natural history of the disorder. The frequency of monoclonal IgMs with functional antibody activity is unknown. The principal problem is detection. New methods have been described which may more precisely identify the antigens reacting with M-proteins. Some "autoimmune" disorders may represent cross-reactions to exogenous antigens. Elucidation of antigens reacting with monoclonal IgM proteins may provide important insights into the pathogenesis of WM.

Coracoid syndrome: a neglected cause of anterior shoulder pain.

PubMed

Gigante, Antonio; Bottegoni, Carlo; Barbadoro, Pamela

2016-01-01

the present prospective open-label study was designed to gain further insights into a condition thought to constitute a neglected but not uncommon syndrome characterized by anterior shoulder pain and tenderness to palpation over the apex of the coracoid process, not related to rotator cuff or pectoralis minor tendinopathy, long head of the biceps tendon disorders, or instability. The aim was to clarify its prevalence, clinical characteristics, differential diagnosis and response to corticosteroid injections. patients with primary anterior shoulder pain precisely reproduced by deep pressure on the apex of the coracoid process were recruited. Patients with clinical or instrumental signs of other shoulder disorders were excluded. Patients were given an injection of triamcinolone acetonide 40 mg/ml 1 ml at the coracoid trigger point. They were evaluated after 15, 30 and 60 days and at 2 years using Equal Visual Analog Scale (EQ-VAS) and the Italian version of the Simple Shoulder Test (SST). between January 1 and December 31 2010, we treated 15 patients aged 26-66 years. The majority were women (86.67%). At 15 days, 6 (40%) patients reported complete resolution of their symptoms, while 9 (60%) complained of residual symptoms and received another injection. At 30 days, 14 (93.33%) patients were pain-free and very satisfied. At 2 years, the 14 patients who had been asymptomatic at 30 days reported that they had experienced no further pain or impaired shoulder function. The analysis of variance for repeated measures showed a significant effect of time on EQ-VAS and SST scores. the present study documents the existence, and characteristics, of a "coracoid syndrome" characterized by anterior shoulder pain and tenderness to palpation over the apex of the coracoid process and showed that the pain is usually amenable to steroid treatment. This syndrome should be clearly distinguished from anterior shoulder pain due to other causes, in order to avoid inappropriate conservative or surgical treatment. Level IV, therapeutic case series.

Validation of the Kohnen Restless Legs Syndrome-Quality of Life instrument.

PubMed

Kohnen, Ralf; Martinez-Martin, Pablo; Benes, Heike; Trenkwalder, Claudia; Högl, Birgit; Dunkl, Elmar; Walters, Arthur S

2016-08-01

Due to the symptoms and the sleep disturbances it causes, Restless Legs Syndrome (RLS) has a negative impact on quality of life. Measurement of such impact can be performed by means of questionnaires, such as the Kohnen Restless Legs Syndrome-Quality of Life questionnaire (KRLS-QoL), a specific 12-item instrument that is self-applied by patients. The present study is aimed at performing a first formal validation study of this instrument. Eight hundred ninety-one patients were included for analysis. RLS severity was assessed by the International Restless Legs Scale (IRLS), Restless Legs Syndrome-6 scales (RLS-6), and Clinical Global Impression of Severity. In addition the Epworth Sleepiness Scale (ESS) was assessed. Acceptability, dimensionality, scaling assumptions, reliability, precision, hypotheses-related validity, and responsiveness were tested. There were missing data in 3.58% patients. Floor and ceiling effects were low for the subscales, global evaluation, and summary index derived from items 1 to 11 after checking that scaling assumptions were met. Exploratory parallel factor analysis showed that the KRLS-QoL may be deemed unidimensional, ie, that all components of the scale are part of one overall general quality of life factor. Indexes of internal consistency (alpha = 0.88), item-total correlation (r S  = 0.32-0.71), item homogeneity coefficient (0.41), and scale stability (ICC = 0.73) demonstrated a satisfactory reliability of the KRLS-QoL. Moderate or high correlations were obtained between KRLS-QoL scores and the IRLS, some components of the RLS-6, inter-KRLS-QoL domains, and global evaluations. Known-groups validity for severity levels grouping and responsiveness analysis results were satisfactory, the latter showing higher magnitudes of response for treated than for placebo arms. The KRLS-QoL was proven an acceptable, reliable, valid, and responsive measure to assess the impact of the RLS on quality of life. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

[Bartter syndrome, severe rare orphan kidney disease: a step towards therapy through pharmacogenetic and epidemiological studies].

PubMed

Conte, Elena; Imbrici, Paola; Sahbani, Dalila; Liantonio, Antonella; Conte, Diana

2018-05-01

Bartter syndromes (BS) types 1-5 are rare salt-losing tubulopathies presenting with overlapping clinical phenotypes including marked salt wasting and hypokalemia leading to polyuria, polydipsia, volume contraction, muscle weakness and growth retardation. These diseases are due to an impairment of sodium, potassium, chloride reabsorption caused by mutations in genes encoding for ion channel or transporters expressed in specific nephron tubule segments. Particularly, BS type 3 is a clinically heterogeneous form caused by mutations in CLCNKB gene which encodes the ClC-Kb chloride channel involved in NaCl reabsorption in the renal tubule. Specific therapy for BS is lacking and the only pharmacotherapy up today available is purely symptomatic and characterized by limiting side effects. The improvement of our understanding of the phenotype/genotype correlation and of the precise pathogenic mechanisms associated with BS type 3 as well as the pharmacological characterization of ClC-K chloride channels are fundamental to design therapies tailored upon patients' mutation. This mini review focused on recent studies representing relevant forward steps in the field as well as noteworthy examples of how basic and clinical research can cooperate to gain insight into the pathophysiology of this renal channelopathy, paving the way for a personalized therapy. Copyright by Società Italiana di Nefrologia SIN, Rome, Italy.

A lethal disease model for New World hantaviruses using immunosuppressed Syrian hamsters.

PubMed

Vergote, Valentijn; Laenen, Lies; Vanmechelen, Bert; Van Ranst, Marc; Verbeken, Erik; Hooper, Jay W; Maes, Piet

2017-10-01

Hantavirus, the hemorrhagic causative agent of two clinical diseases, is found worldwide with variation in severity, incidence and mortality. The most lethal hantaviruses are found on the American continent where the most prevalent viruses like Andes virus and Sin Nombre virus are known to cause hantavirus pulmonary syndrome. New World hantavirus infection of immunocompetent hamsters results in an asymptomatic infection except for Andes virus and Maporal virus; the only hantaviruses causing a lethal disease in immunocompetent Syrian hamsters mimicking hantavirus pulmonary syndrome in humans. Hamsters, immunosuppressed with dexamethasone and cyclophosphamide, were infected intramuscularly with different New World hantavirus strains (Bayou virus, Black Creek Canal virus, Caño Delgadito virus, Choclo virus, Laguna Negra virus, and Maporal virus). In the present study, we show that immunosuppression of hamsters followed by infection with a New World hantavirus results in an acute disease that precisely mimics both hantavirus disease in humans and Andes virus infection of hamsters. Infected hamsters showed specific clinical signs of disease and moreover, histological analysis of lung tissue showed signs of pulmonary edema and inflammation within alveolar septa. In this study, we were able to infect immunosuppressed hamsters with different New World hantaviruses reaching a lethal outcome with signs of disease mimicking human disease.

Failure to detect Xenotropic murine leukaemia virus-related virus in Chinese patients with chronic fatigue syndrome

PubMed Central

2010-01-01

Background Recent controversy has surrounded the question of whether xenotropic murine leukaemia virus-related virus (XMRV) contributes to the pathogenesis of chronic fatigue syndrome (CFS). To investigate the question in a Chinese population, 65 CFS patients and 85 blood donor controls were enrolled and multiplex real-time PCR or reverse transcriptase PCR (RT-PCR) was developed to analyze the XMRV infection status of the study participants. The assay was standardized by constructing plasmid DNAs and armored RNAs as XMRV standards and competitive internal controls (CICs), respectively. Results The sensitivities of the multiplex real-time PCR and RT-PCR assays were 20 copies/reaction and 10 IU/ml, respectively, with 100% specificity. The within-run precision coefficient of variation (CV) ranged from 1.76% to 2.80% and 1.70% to 2.59%, while the between-run CV ranged from 1.07% to 2.56% and 1.06% to 2.74%. XMRV was not detected in the 65 CFS patients and 65 normal individuals out of 85 controls. Conclusions This study failed to show XMRV in peripheral blood mononuclear cells (PBMCs) and plasma of Chinese patients with CFS. The absence of XMRV nucleic acids does not support an association between XMRV infection and the development of CFS in Chinese. PMID:20836869

A case definition and photographic screening tool for the facial phenotype of fetal alcohol syndrome.

PubMed

Astley, S J; Clarren, S K

1996-07-01

The purpose of this study was to demonstrate that a quantitative, multivariate case definition of the fetal alcohol syndrome (FAS) facial phenotype could be derived from photographs of individuals with FAS and to demonstrate how this case definition and photographic approach could be used to develop efficient, accurate, and precise screening tools, diagnostic aids, and possibly surveillance tools. Frontal facial photographs of 42 subjects (from birth to 27 years of age) with FAS were matched to 84 subjects without FAS. The study population was randomly divided in half. Group 1 was used to identify the facial features that best differentiated individuals with and without FAS. Group 2 was used for cross validation. In group 1, stepwise discriminant analysis identified three facial features (reduced palpebral fissure length/inner canthal distance ratio, smooth philtrum, and thin upper lip) as the cluster of features that differentiated individuals with and without FAS in groups 1 and 2 with 100% accuracy. Sensitivity and specificity were unaffected by race, gender, and age. The phenotypic case definition derived from photographs accurately distinguished between individuals with and without FAS, demonstrating the potential of this approach for developing screening, diagnostic, and surveillance tools. Further evaluation of the validity and generalizability of this method will be needed.

A de novo Pericentric Inversion in Chromosome 4 Associated with Disruption of PITX2 and a Microdeletion in 4p15.2 in a Patient with Axenfeld-Rieger Syndrome and Developmental Delay.

PubMed

Maldžienė, Živilė; Preikšaitienė, Eglė; Ignotienė, Salomėja; Kapitanova, Natalija; Utkus, Algirdas; Kučinskas, Vaidutis

2017-01-01

Axenfeld-Rieger syndrome (ARS) is a clinically and genetically heterogeneous group of autosomal dominantly inherited malformations that predominantly affect the eye but are also associated with craniofacial dysmorphism and dental abnormalities. A broad spectrum of genetic alterations involving PITX2 and FOXC1 lead to ARS. We report on a 4-year-old girl with clinical features of ARS and developmental delay due to a de novo apparently balanced pericentric inversion in chromosome 4. This report emphasizes that complementary investigations are necessary to precisely characterize chromosomal rearrangements. Elucidation of the exact genetic cause of ARS is important for comprehensive genetic counseling of the family members and for better patient management. © 2017 S. Karger AG, Basel.

Cancer predisposition syndromes: lessons for truly precision medicine.

PubMed

Glaire, Mark A; Brown, Matthew; Church, David N; Tomlinson, Ian

2017-01-01

Cancer predisposition syndromes are typically uncommon, monogenic, high-penetrance disorders. Despite their rarity, they have proven to be highly clinically relevant in directing cancer prevention strategies. As such, they share notable similarities with an expanding class of low-frequency somatic mutations that are associated with a striking prognostic or predictive effect in the tumours in which they occur. In this review, we highlight these commonalities, with particular reference to mutations in the proofreading domain of replicative DNA polymerases. These molecular phenotypes may occur as either germline or somatic events, and in the latter case, have been shown to confer a favourable prognosis and potential increased benefit from immune checkpoint inhibition. We note that incorporation of these variants into clinical management algorithms will help refine patient management, and that this will be further improved by the inclusion of other germline variants, such as those that determine the likelihood of benefit or toxicity from anti-neoplastic therapy. Finally, we propose that such integrated patient and tumour profiling will be essential if we are to deliver truly precision medicine for cancer patients, but in a similar way to rare germline mutations, we must ensure that we identify and utilize rare somatic mutations with strong predictive and prognostic effects. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Pursuing Precision Speech-Language Therapy Services for Children with Down Syndrome.

PubMed

McDaniel, Jena; Yoder, Paul J

2016-11-01

The behavioral phenotype of individuals with Down syndrome (DS) offers one avenue for developing speech-language therapy services that are tailored to the individual's characteristics that affect treatment response. Behavioral phenotypes are patterns of behavioral strengths and weaknesses for specific genetic disorders that can help guide the development and implementation of effective interventions. Nonetheless, individual differences within children with DS must be acknowledged and addressed because behavioral phenotypes are probabilistic, not deterministic. Developing precision speech-language therapy services to maximize learning opportunities and outcomes for children with DS calls for increased collaboration among clinicians and researchers to address the needs, challenges, and opportunities on three interconnected themes: (1) moving effective interventions from research to practice, (2) making evidence-based, child-specific treatment intensity decisions, and (3) considering child motivation and temperament characteristics. Increased availability of intervention materials and resources as well as more specific recommendations that acknowledge individual differences could help narrow the research-practice gap. Clear descriptions of disciplined manipulations of treatment intensity components could lead to more effective intervention services. Last, addressing motivation and temperament characteristics, such as the personality-motivation orientation, in children with DS may help maximize learning opportunities. Focused attention and collaboration on these key themes could produce substantial, positive changes for children with DS and their families in the coming decade. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

An epigenomics approach to individual differences and its translation to neuropsychiatric conditions.

PubMed

Sweatt, J David; Tamminga, Carol A

2016-09-01

This review concerns epigenetic mechanisms and their roles in conferring interindividual differences, especially as related to experientially acquired and genetically driven changes in central nervous system (CNS) function. In addition, the review contains commentary regarding the possible ways in which epigenomic changes may contribute to neuropsychiatric conditions and disorders and ways in which epigenotyping might be cross-correlated with clinical phenotyping in the context of precision medicine. The review begins with a basic description of epigenetic marking in the CNS and how these changes are powerful regulators of gene readout. Means for characterizing the individual epigenotype are briefly described, with a focus on DNA cytosine methylation as a readily measurable, stable epigenetic mark. This background enables a discussion of how "epigenotyping" might be integrated along with genotyping and deep phenotyping as a means of implementing advanced precision medicine. Finally, the commentary addresses two exemplars when considering how epigenotype may correlate with and modulate cognitive and behavioral phenotype: schizophrenia and Rett syndrome. These two disorders provide an interesting compare-and-contrast example regarding possible epigenotypic regulation of behavior: whereas Rett syndrome is clearly established as being caused by disruption of the function of an epigenetic "reader" of the DNA cytosine methylome-methyl-CpG-binding protein 2 (MeCP2)-the case for a role for epigenetic mechanisms in schizophrenia is still quite speculative.

Using Marginal Structural Measurement-Error Models to Estimate the Long-term Effect of Antiretroviral Therapy on Incident AIDS or Death

PubMed Central

Cole, Stephen R.; Jacobson, Lisa P.; Tien, Phyllis C.; Kingsley, Lawrence; Chmiel, Joan S.; Anastos, Kathryn

2010-01-01

To estimate the net effect of imperfectly measured highly active antiretroviral therapy on incident acquired immunodeficiency syndrome or death, the authors combined inverse probability-of-treatment-and-censoring weighted estimation of a marginal structural Cox model with regression-calibration methods. Between 1995 and 2007, 950 human immunodeficiency virus–positive men and women were followed in 2 US cohort studies. During 4,054 person-years, 374 initiated highly active antiretroviral therapy, 211 developed acquired immunodeficiency syndrome or died, and 173 dropped out. Accounting for measured confounders and determinants of dropout, the weighted hazard ratio for acquired immunodeficiency syndrome or death comparing use of highly active antiretroviral therapy in the prior 2 years with no therapy was 0.36 (95% confidence limits: 0.21, 0.61). This association was relatively constant over follow-up (P = 0.19) and stronger than crude or adjusted hazard ratios of 0.75 and 0.95, respectively. Accounting for measurement error in reported exposure using external validation data on 331 men and women provided a hazard ratio of 0.17, with bias shifted from the hazard ratio to the estimate of precision as seen by the 2.5-fold wider confidence limits (95% confidence limits: 0.06, 0.43). Marginal structural measurement-error models can simultaneously account for 3 major sources of bias in epidemiologic research: validated exposure measurement error, measured selection bias, and measured time-fixed and time-varying confounding. PMID:19934191

Muscle 'contractures' and the 'stiff-man' syndrome.

PubMed

Slater, J D

1986-12-01

The aetiology of the clinical stiff-man syndrome is likely to be heterogenous, but until we have more precise methods of identifying an individual cause the need will continue for this rather flippant appellation in patients whose condition cannot be described in any other way. It is also important because patients may otherwise become labelled as suffering from a psychiatric disorder and may even be falsely accused of abusing diazepam (Westblom, 1978). The reverse is also true, and patients may masquerade as stiff men or women (Price and Allott, 1958; Casati and Rossi, 1969). The endocrine dimension remains and should be tested for carefully, particularly in patients with predominantly lower-limb rigidity whose spasms are a relatively minor aspect of their clinical syndrome. Clearly those patients described by George et al (1984) and Slater (1960) as suffering from the stiff-man syndrome need to be reclassified as examples of the hormonal stiff muscle syndrome, and there may be others so misclassified. An endocrine aetiology may easily be missed in a patient with relatively minor muscle stiffness, pain and cramps, such as the man described by Yunus et al (1981) whose myalgia, 'arthralgia' and muscle tenderness vanished completely within four days of taking physiological replacement doses of cortisone acetate as treatment for his hypopituitarism. The rarity of the stiff-man syndrome makes prospective studies of its aetiology and treatment impossible, yet the dramatic and devastating nature of the syndrome suggests that such cases may be extreme examples of a much more common condition. On the other hand, it is possible to argue that once the psychiatric, the overtly neurological and the endocrine cases are omitted we are left with nothing. However, this is just where Moersch and Woltman came in; they could not explain 14 of their cases. Despite modern technology, despite refinements of diagnosis and despite the increasing recognition of the stiff-man syndrome as a heterogeneous condition, there still remains--albeit very rarely--a cohort of patients with progressive proximal muscular stiffness and spasms who defy proper scientific explanation, but who are likely to suffer from a chronic myelitis which destroys normal feedback mechanisms between muscle spindles and the spinal cord. Experience over the last 30 years has served at least to alert people to the psychiatric possibilities, to remove any question of primary muscle or tendon disease and to point to the usefulness of diazepam. With hope, this chapter provides an endocrine dimension which offers an actual cure and therefore deserves to be more widely recognized.

Body composition, metabolism, sleep, psychological and eating patterns of overtraining syndrome: Results of the EROS study (EROS-PROFILE).

PubMed

Cadegiani, Flavio A; Kater, Claudio E

2018-08-01

Overtraining syndrome (OTS) is caused by an imbalance between training, nutrition and resting, and leads to decreased performance and fatigue; however, the precise underlying triggers of OTS remain unclear. This study investigated the body composition, metabolism, eating, sleeping patterns and mood states among participants with OTS. Selected participants were divided into OTS-affected athletes (OTS, n = 14), healthy athletes (ATL, n = 25), and healthy non-physically active controls (NCS, n = 12). Compared to ATL, OTS showed decreased sleep quality (p = 0.004); increased duration of work or study (p < 0.001); decreased libido (p = 0.024); decreased calorie (p < 0.001), carbohydrate (p < 0.001) and protein (p < 0.001) intakes; decreased mood states (p < 0.001); decreased basal metabolic rate (p = 0.013) and fat burning (p < 0.001); increased body fat (p = 0.006); decreased muscle mass (p = 0.008); and decreased hydration (p < 0.001). Levels were similar between OTS and NCS, except for worsened fatigue (p < 0.001) and vigour (p = 0.001) in OTS. Reduced calorie intake, worsened sleep, and increased cognitive activity are likely OTS triggers. OTS appears to induce dehydration, increase body fat, decrease libido, and worsen mood.

Risk factors for recurrence of venous thromboembolism associated with the use of oral contraceptives.

PubMed

Vaillant-Roussel, Hélène; Ouchchane, Lemlih; Dauphin, Claire; Philippe, Pierre; Ruivard, Marc

2011-11-01

Combined oral contraceptives (COC) increase the risk of venous thromboembolism (VTE), but the risk of recurrent VTE is not precisely determined. In this retrospective cohort study, we sought the risk factors for recurrence after a first VTE that occurred in women taking COC. Time-to-event analysis was done with Kaplan-Meier estimates. In total, 172 patients were included (43% with pulmonary embolism): 82% had no other clinical risk factor for VTE. Among the 160 patients who stopped anticoagulation, the cumulative incidence of recurrent VTE was 5.1% after 1 year and 14.2% after 5 years. Significant factors associated with recurrence were renewed use of COC [hazard ratio (HR)=8.2 (2.1-32.2)], antiphospholipid syndrome [HR=4.1 (1.3-12.5)] and protein C deficiency or factor II G20210A [HR=2.7 (1.1-7)]. Pure-progestin contraception [HR=1.3 (0.5-3.0)] or factor V Leiden [HR=1.3 (0.5-3.4)] did not increase recurrence. Postsurgical VTE had a lower risk of recurrence [HR=0.1 (0.0-0.9)]. Further studies are warranted to determine whether testing for antiphospholipid syndrome, protein C deficiency or the factor II G20210A could modify the duration of anticoagulation. This study confirms the safety of pure-progestin contraception. Copyright © 2011 Elsevier Inc. All rights reserved.

A patient with heart failure and worsening kidney function.

PubMed

Sarnak, Mark J

2014-10-07

There is high prevalence of CKD, defined by reduced GFR, in patients with heart failure. Reduced kidney function is associated with increased morbidity and mortality in this patient population. The cardiorenal syndrome (CRS) involves a bidirectional relationship between the heart and kidneys whereby dysfunction in either may exacerbate the function of the other, but this syndrome has been difficult to precisely define because it has many complex physiologic, biochemical, and hormonal abnormalities. The pathophysiology of CRS is not completely understood, but potential mechanisms include reduced kidney perfusion due to decreased forward flow, increased right ventricular and venous pressure, and neurohormonal adaptations. Treatment options include inotropic medications; diuretics; ultrafiltration; and medications, such as β-blockers, inhibitors of the renin-angiotensin-aldosterone system, and more novel treatments that focus on unique aspects of the pathophysiology. Recent observational studies suggest that treatments that result in a decrease in venous pressure and lead to hemoconcentration may be associated with improved outcomes. Patients with CRS that is not responsive to medical interventions should be considered for ventricular assist devices, heart transplantation, or combined heart and kidney transplantation. Copyright © 2014 by the American Society of Nephrology.

A genetic linkage map of the long arm of human chromosome 22.

PubMed

Rouleau, G A; Haines, J L; Bazanowski, A; Colella-Crowley, A; Trofatter, J A; Wexler, N S; Conneally, P M; Gusella, J F

1989-01-01

We have used a recombinant phage library enriched for chromosome 22 sequences to isolate and characterize eight anonymous DNA probes detecting restriction fragment length polymorphisms on this autosome. These were used in conjunction with eight previously reported loci, including the genes BCR, IGLV, and PDGFB, four anonymous DNA markers, and the P1 blood group antigen, to construct a linkage map for chromosome 22. The linkage group is surprisingly large, spanning 97 cM on the long arm of the chromosome. There are no large gaps in the map; the largest intermarker interval is 14 cM. Unlike several other chromosomes, little overall difference was observed for sex-specific recombination rates on chromosome 22. The availability of a genetic map will facilitate investigation of chromosome 22 rearrangements in such disorders as cat eye syndrome and DiGeorge syndrome, deletions in acoustic neuroma and meningioma, and translocations in Ewing sarcoma. This defined set of linked markers will also permit testing chromosome 22 for the presence of particular disease genes by family studies and should immediately support more precise mapping and identification of flanking markers for NF2, the defective gene causing bilateral acoustic neurofibromatosis.

An examination of the vibration transmissibility of the hand-arm system in three orthogonal directions.

PubMed

Welcome, Daniel E; Dong, Ren G; Xu, Xueyan S; Warren, Christopher; McDowell, Thomas W; Wu, John Z

2015-02-01

The objective of this study is to enhance the understanding of the vibration transmission in the hand-arm system in three orthogonal directions ( X, Y , and Z ). For the first time, the transmitted vibrations distributed on the entire hand-arm system exposed in the three orthogonal directions via a 3-D vibration test system were measured using a 3-D laser vibrometer. Seven adult male subjects participated in the experiment. This study confirms that the vibration transmissibility generally decreased with the increase in distance from the hand and it varied with the vibration direction. Specifically, to the upper arm and shoulder, only moderate vibration transmission was measured in the test frequency range (16 to 500 Hz), and virtually no transmission was measured in the frequency range higher than 50 Hz. The resonance vibration on the forearm was primarily in the range of 16-30 Hz with the peak amplitude of approximately 1.5 times of the input vibration amplitude. The major resonance on the dorsal surfaces of the hand and wrist occurred at around 30-40 Hz and, in the Y direction, with peak amplitude of more than 2.5 times of the input amplitude. At higher than 50 Hz, vibration transmission was effectively limited to the hand and fingers. A major finger resonance was observed at around 100 Hz in the X and Y directions and around 200 Hz in the Z direction. In the fingers, the resonance magnitude in the Z direction was generally the lowest, and the resonance magnitude in the Y direction was generally the highest with the resonance amplitude of 3 times the input vibration, which was similar to the transmissibility at the wrist and hand dorsum. The implications of the results are discussed. Prolonged, intensive exposure to hand-transmitted vibration could result in hand-arm vibration syndrome. While the syndrome's precise mechanisms remain unclear, the characterization of the vibration transmissibility of the system in the three orthogonal dimensions performed in this study can help understand the syndrome and help develop improved frequency weightings for assessing the risk of the exposure for developing various components of the syndrome.

An examination of the vibration transmissibility of the hand-arm system in three orthogonal directions

PubMed Central

Welcome, Daniel E.; Dong, Ren G.; Xu, Xueyan S.; Warren, Christopher; McDowell, Thomas W.; Wu, John Z.

2015-01-01

The objective of this study is to enhance the understanding of the vibration transmission in the hand-arm system in three orthogonal directions (X, Y, and Z). For the first time, the transmitted vibrations distributed on the entire hand-arm system exposed in the three orthogonal directions via a 3-D vibration test system were measured using a 3-D laser vibrometer. Seven adult male subjects participated in the experiment. This study confirms that the vibration transmissibility generally decreased with the increase in distance from the hand and it varied with the vibration direction. Specifically, to the upper arm and shoulder, only moderate vibration transmission was measured in the test frequency range (16 to 500 Hz), and virtually no transmission was measured in the frequency range higher than 50 Hz. The resonance vibration on the forearm was primarily in the range of 16–30 Hz with the peak amplitude of approximately 1.5 times of the input vibration amplitude. The major resonance on the dorsal surfaces of the hand and wrist occurred at around 30–40 Hz and, in the Y direction, with peak amplitude of more than 2.5 times of the input amplitude. At higher than 50 Hz, vibration transmission was effectively limited to the hand and fingers. A major finger resonance was observed at around 100 Hz in the X and Y directions and around 200 Hz in the Z direction. In the fingers, the resonance magnitude in the Z direction was generally the lowest, and the resonance magnitude in the Y direction was generally the highest with the resonance amplitude of 3 times the input vibration, which was similar to the transmissibility at the wrist and hand dorsum. The implications of the results are discussed. Relevance to industry Prolonged, intensive exposure to hand-transmitted vibration could result in hand-arm vibration syndrome. While the syndrome's precise mechanisms remain unclear, the characterization of the vibration transmissibility of the system in the three orthogonal dimensions performed in this study can help understand the syndrome and help develop improved frequency weightings for assessing the risk of the exposure for developing various components of the syndrome. PMID:26635424

Specialized Pro-resolving Mediators Regulate Alveolar Fluid Clearance during Acute Respiratory Distress Syndrome

PubMed Central

Wang, Qian; Yan, Song-Fan; Hao, Yu; Jin, Sheng-Wei

2018-01-01

Objective: Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS. Data Sources: Articles published up to September 2017 were selected from the PubMed, with the keywords of “alveolar fluid clearance” or “lung edema” or “acute lung injury” or “acute respiratory distress syndrome”, and “specialized pro-resolving mediators” or “lipoxin” or “resolvin” or “protectin” or “maresin” or “alveolar epithelial cells” or “aspirin-triggered lipid mediators” or “carbon monoxide and heme oxygenase” or “annexin A1”. Study Selection: We included all relevant articles published up to September 2017, with no limitation of study design. Results: Specialized pro-resolving mediators (SPMs), as the proinflammatory mediators, not only upregulated epithelial sodium channel, Na,K-ATPase, cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporins levels, but also improved Na,K-ATPase activity to promote AFC in ARDS. In addition to the direct effects on ion channels and pumps of the alveolar epithelium, the SPMs also inhibited the inflammatory cytokine expression and improved the alveolar epithelial cell repair to enhance the AFC in ARDS. Conclusions: The present review discusses a novel mechanism for pulmonary edema fluid reabsorption. SPMs might provide new opportunities to design “reabsorption-targeted” therapies with high degrees of precision in controlling ALI/ARDS. PMID:29664060

The origins and drivers of insulin resistance.

PubMed

Johnson, Andrew M F; Olefsky, Jerrold M

2013-02-14

Obesity-induced insulin resistance is the major determinant of metabolic syndrome, which precedes the development of type 2 diabetes mellitus and is thus the driving force behind the emerging diabetes epidemic. The precise causes of insulin resistance are varied, and the relative importance of each is a matter of ongoing research. Here, we offer a Perspective on the heterogeneous etiology of insulin resistance, focusing in particular on the role of inflammation, lipid metabolism, and the gastrointestinal microbiota. Copyright © 2013 Elsevier Inc. All rights reserved.

Biology of obesity: lessons from animal models of obesity.

PubMed

Kanasaki, Keizo; Koya, Daisuke

2011-01-01

Obesity is an epidemic problem in the world and is associated with several health problems, including diabetes, cardiovascular disease, respiratory failure, muscle weakness, and cancer. The precise molecular mechanisms by which obesity induces these health problems are not yet clear. To better understand the pathomechanisms of human disease, good animal models are essential. In this paper, we will analyze animal models of obesity and their use in the research of obesity-associated human health conditions and diseases such as diabetes, cancer, and obstructive sleep apnea syndrome.

Camus's L'étranger and the first description of a man with Asperger's syndrome.

PubMed

Shuster, Sam

2018-01-01

The continued discussion about the meaning of Camus's famous novel, L'étranger , provoked a re-reading, and this, in turn, led to its clinical analysis and further investigation. The book rests entirely on the thoughts, words and actions of its central character, Meursault, and these were found to show impairment of social relationships, communication and interaction, with other traits diagnostic of the Asperger's subgroup of the autism spectrum disorder. It was then found that Camus had based Meursault on his close friend Galindo, and a search was therefore made for evidence of Galindo's character; this revealed him to be an intelligent but odd person, who exhibited the characteristic impairment of social and personal behavior of Asperger's syndrome. Thus, Camus had recognized and understood his friend's strange behavior before Asperger's syndrome had been defined; his use of it for the creation of Meursault is therefore the first published account of a man with this disorder. Many of the interpretations and ideas developed from Meursault's words, thoughts and actions must now be reconsidered, as they are a misreading of the words and behavior of a man with Asperger's syndrome. The outcome of this clinical examination of L'étranger is unique; it shows that a precise account of a person with a neurobehavioral disorder was made by a novelist before the disorder had been clinically defined.

Molecular mapping of the Edwards syndrome phenotype to two noncontiguous regions on chromosome 18

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boghosian-Sell, L.; Mewar, R.; Harrison, W.

1994-09-01

In an effort to identify regions on chromosome 18 that may be critical in the appearance of the Edwards syndrome phenotype, the authors have analyzed six patients with partial duplication of chromosome 18. Four of the patients have duplications involving the distal half of 18q (18q21.1-qter) and are very mildly affected. The remaining two patients have most of 18q (18q12.1-qter) duplicated, are severely affected, and have been diagnosed with Edwards syndrome. The authors have employed FISH, using DNA probes from a chromosome 18-specific library, for the precise determination of the duplicated material in each of these patients. The clinical featuresmore » and the extent of the chromosomal duplication in these patients were compared with four previously reported partial trisomy 18 patients, to identify regions of chromosome 18 that may be responsible for certain clinical features of trisomy 18. The comparative analysis confirmed that there is no single region on 18q that is sufficient to produce the trisomy 18 phenotype and identified two regions on 18q that may work in conjunction to produce the Edwards syndrome phenotype. In addition, correlative analysis indicates that duplication of 18q12.3-q22.1 may be associated with more severe mental retardation in trisomy 18 individuals. 25 refs., 3 figs., 1 tab.« less

Kidney-Heart Interactions in Acute Kidney Injury.

PubMed

Doi, Kent

2016-01-01

Acute kidney injury (AKI) is a common complication in critically ill patients treated in intensive care units. Renal replacement therapy (RRT)-requiring AKI occurs in approximately 5-10% patients in intensive care unit and their mortality rate is unacceptably high (50-60%), despite sufficient control of uremia using remarkably advanced modern RRT techniques. This suggests that there are unrecognized organ interactions following AKI that could worsen the outcomes. Cardiorenal syndrome has been defined based on clinical observations that acute and chronic heart failure causes kidney injury and AKI and that chronic kidney disease worsens heart diseases. Possible pathways that connect these 2 organs have been suggested; however, the precise mechanisms are yet to be clarified, particularly in AKI-induced cardiac dysfunction. This review focuses on acute cardiac dysfunction in the setting of AKI. A recent animal study demonstrated the dysregulation of mitochondrial dynamics caused by an increased dynamin-related protein 1 expression and cellular apoptosis of the heart in a renal ischemia reperfusion model. Although the precise mechanisms that induce cardiac mitochondrial injury in AKI remain unclear, cardiac mitochondria injury could be a novel candidate of drug targets against high mortality in severe AKI. © 2016 S. Karger AG, Basel.

Intrathecal baclofen: effects on spasticity, pain, and consciousness in disorders of consciousness and locked-in syndrome.

PubMed

Pistoia, Francesca; Sacco, Simona; Sarà, Marco; Franceschini, Marco; Carolei, Antonio

2015-01-01

Disorders of consciousness (DOCs) include coma, vegetative state (VS), and minimally conscious state (MCS). Coma is characterized by impaired wakefulness and consciousness, while VS and MCS are defined by lacking or discontinuous consciousness despite recovered wakefulness. Conversely, locked-in syndrome (LIS) is characterized by quadriplegia and lower cranial nerve paralysis with preserved consciousness. Intrathecal baclofen (ITB) is a useful treatment to improve spasticity both in patients with DOCs and LIS. Moreover, it supports the recovery of consciousness in some patients with VS or MCS. The precise mechanism underlying this recovery has not yet been elucidated. It has been hypothesized that ITB may act by reducing the overload of dysfunctional sensory stimuli reaching the injured brain or by stabilizing the imbalanced circadian rhythms. Although the current indication of ITB is the management of severe spasticity, its potential use in speeding the recovery of consciousness merits further investigation.

Systemic lupus erythematosus with organic brain syndrome: serial electroencephalograms accurately evaluate therapeutic efficacy.

PubMed

Kato, Takashi; Shiratori, Kyoji; Kobashigawa, Tsuyoshi; Hidaka, Yuji

2006-01-01

A 48-year-old man with systemic lupus erythematosus developed organic brain syndrome. High-dose prednisolone was ineffective, and somnolence without focal signs rapidly developed. Electroencephalogram (EEG) demonstrated a slow basic rhythm (3 Hz), but brain magnetic resonance imaging was normal. Somnolence resolved soon after performing plasma exchange (two sessions). However, memory dysfunction persisted, with EEG demonstrating mild abnormalities (7-8 Hz basic rhythm). Double-filtration plasmapheresis (three sessions) was done, followed by intravenous cyclophosphamide. Immediately after the first plasmapheresis session, memory dysfunction began to improve. After the second dose of cyclophosphamide, intellectual function resolved completely and EEG findings also normalized (basic rhythm of 10 Hz waves). Serial EEG findings precisely reflected the neurological condition and therapeutic efficacy in this patient. In contrast, protein levels in cerebrospinal fluid remained high and did not seem to appropriately reflect the neurological condition in this patient.

Lewy Body Disease: Clinical and Pathological "Overlap Syndrome" Between Synucleinopathies (Parkinson Disease) and Tauopathies (Alzheimer Disease).

PubMed

Foguem, Clovis; Manckoundia, Patrick

2018-04-08

Lewy body disease (LBD) is a neurodegenerative disease resulting in dementia. It shares clinical and pathological features with Parkinson disease (PD), the most frequent synucleinopathy, Parkinson disease dementia (PDD), and Alzheimer disease (AD), a tauopathy. Even though the diagnostic criteria for these neurodegenerative diseases are clearly established, and recently revised for LBD, their precise clinical diagnosis is often difficult because LBD, PD, PDD, and AD share epidemiological, clinical, and pathological characteristics. This manuscript discusses current understanding of overlapping symptoms and the particular features of LBD, PD, and AD. It also describes features that could facilitate the diagnosis of each of these diseases. We concluded that the concept of neurodegenerative "overlap" syndrome, which includes the accepted diagnosis of LBD, may be taken in account and should contribute to clarifying LBD and definitions of close differential diagnoses. This should allow clinicians to suspect LBD at an earlier stage and provide better patient care.

A Precision Medicine Approach to the Rescue of Function on Malignant Calmodulinopathic Long-QT Syndrome.

PubMed

Limpitikul, Worawan B; Dick, Ivy E; Tester, David J; Boczek, Nicole J; Limphong, Pattraranee; Yang, Wanjun; Choi, Myoung Hyun; Babich, Jennifer; DiSilvestre, Deborah; Kanter, Ronald J; Tomaselli, Gordon F; Ackerman, Michael J; Yue, David T

2017-01-06

Calmodulinopathies comprise a new category of potentially life-threatening genetic arrhythmia syndromes capable of producing severe long-QT syndrome (LQTS) with mutations involving CALM1, CALM2, or CALM3. The underlying basis of this form of LQTS is a disruption of Ca 2+ /calmodulin (CaM)-dependent inactivation of L-type Ca 2+ channels. To gain insight into the mechanistic underpinnings of calmodulinopathies and devise new therapeutic strategies for the treatment of this form of LQTS. We generated and characterized the functional properties of induced pluripotent stem cell-derived cardiomyocytes from a patient with D130G-CALM2-mediated LQTS, thus creating a platform with which to devise and test novel therapeutic strategies. The patient-derived induced pluripotent stem cell-derived cardiomyocytes display (1) significantly prolonged action potentials, (2) disrupted Ca 2+ cycling properties, and (3) diminished Ca 2+ /CaM-dependent inactivation of L-type Ca 2+ channels. Next, taking advantage of the fact that calmodulinopathy patients harbor a mutation in only 1 of 6 redundant CaM-encoding alleles, we devised a strategy using CRISPR interference to selectively suppress the mutant gene while sparing the wild-type counterparts. Indeed, suppression of CALM2 expression produced a functional rescue in induced pluripotent stem cell-derived cardiomyocytes with D130G-CALM2, as shown by the normalization of action potential duration and Ca 2+ /CaM-dependent inactivation after treatment. Moreover, CRISPR interference can be designed to achieve selective knockdown of any of the 3 CALM genes, making it a generalizable therapeutic strategy for any calmodulinopathy. Overall, this therapeutic strategy holds great promise for calmodulinopathy patients as it represents a generalizable intervention capable of specifically altering CaM expression and potentially attenuating LQTS-triggered cardiac events, thus initiating a path toward precision medicine. © 2016 American Heart Association, Inc.

[Demons and Meigs syndromes and pseudosyndromes today].

PubMed

Brun, G-H

2010-05-01

There is a total confusion between Demons or Meigs syndromes and pseudosyndromes.The need for greater precision in publications titles has become an emergency. We have analysed 297 observations gathered in litterature from 1904 to 2004. The increase in the number of Meigs pseudosyndromes based on diverse associated condition means that we must include under the name Demons syndrome, as he did himself, all tumours of the female genital tract, providing they are benign, wherever the effusion takes place, reserve the name Demons Meigs because it has been used historically and because it was Meigs wish, solely for fibrothecomas of the ovary and for tumours of the granulosa bring together under the name Demons pseudosyndrome all other non tumoral benign entities. Malignant tumours, with or without malignant cells in the effusions are not pseudosyndromes but authentic neoplastic lesions. An over-lax definition of pseudosyndromes runs the risk of the name simply becoming a catch-all term. On the other hand we can say that 100years later diagnosis is not earlier, a bilateral tumor is not a rarity, mechanisms of effusions genesis remain mysterious and the treatment has been enriched with coeliosurgery. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Clinical pictures of unknown origin in neurology: past, present and future usefulness of artificial intelligence.

PubMed

Conti, Andrea A; Conti, Antonio; Masoni, Marco; Gensini, Gian Franco

2005-01-01

Although, in the course of the last 50 years, the achievements in the medical field have been astonishing, at the beginning of the third millennium a number of clinical pictures are still left without a precise nosographic origin. In the past, the delay in scientific communication was the main explanation presented for the lack of understanding of clinical pictures of unknown nosographic origin. The history of medicine provides excellent examples of this dispersion of human capital, even if the history of clinical neurology presents "exceptions" (the pictures that we now call de la Tourette's syndrome and Parkinson's disease) that indicate that major clinical syndromes could be clearly detected and relatively rapidly diffused even in the 19th century. Contrary to the past, the delay in scientific communication no longer seems an obstacle to the sharing of medical knowledge. Nevertheless, the problem of the in-depth comprehension of clinical pictures of unknown nosographic origin still remains dominant, mainly because of the limited spread of ample and flexible online accessible databases of unknown nosographic origin clinical syndromes. The need for interactive electronic archives and other artificial intelligence resources in order to promote progress in clinical knowledge is discussed in this paper.

[Main principles of rapid diagnosis and intensive care in emergency states: their realization in expert systems].

PubMed

Zislin, B D; Bazhenov, A M; Belkin, A A; Bazylev, S V; Badaev, F I; Trifonov, Iu O

1997-01-01

A retrospective analysis of 543 case histories over 1980-1990 in the town of Yekaterinburg and analysis of published data permitted the authors to single out the signs characterizing the most frequent syndromes requiring urgent intensive care. By either diagnostic value, these signs are distributed into main, accessory, and ruling out. An expert system has been created, making use of the productive-Freimont's approach to representing information on the basis of blurred multiplicities and ambiguous logics. The diagnosis was made by stages: first the main signs were analyzed, determining the severity of patient's status, then (after first aid was rendered) accessory and ruling out signs, which help make the diagnosis more precise. The system was tried in 231 patients, 102 of these with acute respiratory failure, 63 with acute hemodynamic insufficiency, and 66 with acute cerebral insufficiency. Primary diagnosis of the underlying syndrome was correct in 87-89% of cases, of the concomitant syndrome in 92-97%. Repeated evaluations (in 1-3 and 24 h) taking account of the time course of the symptoms and of the results of unsophisticated instrumental examinations increased the share of correct diagnoses to 92-96%.

Can metabolic side effects of antipsychotics be reversed by lifestyle changes?

PubMed

Bolger, Alistair; Verdolini, Norma; Agius, Mark

2014-11-01

Antipsychotics, particularly atypical antipsychotics, are known to have metabolic side effects such as; weight gain, hyperlipidaemia and insulin resistance. This is problematic as metabolic syndrome can be a precursor to many diseases, including type II diabetes and coronary heart disease. In an attempt to overcome these side-effects, lifestyle changes have been recommended in tandem with commencement of atypical antipsychotics, but is this effective at halting metabolic syndrome? There is some evidence suggesting that lifestyle changes can reduce weight gain caused by atypical antipsychotics. However, there seems to be a paucity of evidence about whether this correlates with correction of metabolic dysregulation. Moreover, there is a lack of research into the precise mechanism of metabolic syndrome as caused by atypical antipsychotics,as well as a lack of evidence into how exercise remedies this. Furthermore, there is research to suggest that the pathophysiology of psychosis may lead to metabolic dysregulation independently of treatment. Lifestyle changes should still be part of a treatment as they seem to partially reverse metabolic changes seen with atypical antipsychotics. However, more research is needed to identify weight independent mechanisms for metabolic dysregulation seen in those taking atypical antipsychotics in order to solve this pressing issue.

Female Gender Scheme is Disturbed by Polycystic Ovary Syndrome: A Qualitative Study From Iran.

PubMed

Nasiri Amiri, Fatemeh; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Mohammadpour Thamtan, Reza Ali; Shiva, Niloofar

2014-02-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting up to one in every five women of reproductive age. The majority of researches on PCOS focus on its biomedical aspects, often overlooking and neglecting women's own perceptions and experiences. This study aimed to explore women's perception and experiences that influence their personal gender role. This research is a qualitative study by conventional content analysis. Semi-structured interviews were conducted with 23 reproductive aged women with PCOS, recruited from the reproductive endocrinology research center. , in-depth interviews were continued to reach data saturation. The study was carried out at the reproductive endocrinology research center of Shahid Beheshti University in Tehran All the interviews were recorded and transcribed, and qualitative content analysis of the data was conducted manually. Four themes were identified. Content analysis of the interviews revealed these women mainly perceived themselves with lack of physical attractiveness, loss of womanhood, interruption of sexual role and disruption of fertility potential, feelings were related to symptoms e.g. 'excess' hair; absent or disrupted menstrual cycle, obesity and infertility commonly experienced by women with PCOS. Women with PCOS are challenged in their perceptions of themselves as "feminine" because of their hairy appearance, irregular menses and lack of fertility and this influences their gender roles. Medical practitioners must understand how PCOS precisely affects women's roles and initiate management aimed at reconstructing their "womanhood", along with their medical treatment.

Female Gender Scheme is Disturbed by Polycystic Ovary Syndrome: A Qualitative Study From Iran

PubMed Central

Nasiri Amiri, Fatemeh; Ramezani Tehrani, Fahimeh; Simbar, Masoumeh; Mohammadpour Thamtan, Reza Ali; Shiva, Niloofar

2014-01-01

Background: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting up to one in every five women of reproductive age. The majority of researches on PCOS focus on its biomedical aspects, often overlooking and neglecting women’s own perceptions and experiences. Objectives: This study aimed to explore women’s perception and experiences that influence their personal gender role. Patients and Methods: This research is a qualitative study by conventional content analysis. Semi-structured interviews were conducted with 23 reproductive aged women with PCOS, recruited from the reproductive endocrinology research center. , in-depth interviews were continued to reach data saturation. The study was carried out at the reproductive endocrinology research center of Shahid Beheshti University in Tehran All the interviews were recorded and transcribed, and qualitative content analysis of the data was conducted manually. Results: Four themes were identified. Content analysis of the interviews revealed these women mainly perceived themselves with lack of physical attractiveness, loss of womanhood, interruption of sexual role and disruption of fertility potential, feelings were related to symptoms e.g. ‘excess’ hair; absent or disrupted menstrual cycle, obesity and infertility commonly experienced by women with PCOS. Conclusions: Women with PCOS are challenged in their perceptions of themselves as “feminine” because of their hairy appearance, irregular menses and lack of fertility and this influences their gender roles. Medical practitioners must understand how PCOS precisely affects women’s roles and initiate management aimed at reconstructing their “womanhood”, along with their medical treatment. PMID:24719724

Nutritional aspects of Noonan syndrome and Noonan-related disorders.

PubMed

da Silva, Fernanda Marchetto; Jorge, Alexander Augusto; Malaquias, Alexandra; da Costa Pereira, Alexandre; Yamamoto, Guilherme Lopes; Kim, Chong Ae; Bertola, Debora

2016-06-01

Rasopathies are a group of rare disorders characterized by neurocardiofaciocutaneous involvement, and caused by mutations in several genes of the RAS/MAPK pathway. In the present study, we characterized growth parameters, body composition, and nutritional aspects of children and adults (n = 62) affected by these disorders, mainly Noonan syndrome, using an indirect method-anthropometry-and a 24-hr recall questionnaire. The growth parameters in our cohort showed short stature, especially in individuals with RAF1 and SHOC2 mutations, lower obesity rates compared to the control population, and BMI scores highest in individuals with BRAF mutations and lowest in individuals with SHOC2. Body composition showed a compromise in the upper arm muscle circumference, with a statistically significant difference in the z-score of triceps skinfold (P = 0.0204) and upper arm fat area (P = 0.0388) between BRAF and SHOC2 groups and in the z-score of triceps skinfold between RAF1 and SHOC2 (P = 0.0218). The pattern of macronutrient consumption was similar to the control population. Our study is the first to address body composition in RASopathy individuals and the data indicate a compromise not only in adipose tissue, but also in muscle mass. Studies using different techniques, such as dual-energy X-ray absorptiometry or imaging studies, which give a more precise delineation of fat and non-fat mass, are required to confirm our results, ultimately causing an impact on management strategies. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Counting or Chunking?

PubMed Central

Spotorno, Nicola; McMillan, Corey T.; Powers, John P.; Clark, Robin; Grossman, Murray

2014-01-01

A growing amount of empirical data is showing that the ability to manipulate quantities in a precise and efficient fashion is rooted in cognitive mechanisms devoted to specific aspects of numbers processing. The Analog number system (ANS) has a reasonable representation of quantities up to about 4, and represents larger quantities on the basis of a numerical ratio between quantities. In order to represent the precise cardinality of a number, the ANS may be supported by external algorithms such as language, leading to a “Precise Number System”. In the setting of limited language, other number-related systems can appear. For example the Parallel Individuation system (PIS) supports a “chunking mechanism” that clusters units of larger numerosities into smaller subsets. In the present study we investigated number processing in non-aphasic patients with Corticobasal Syndrome (CBS) and Posterior Cortical Atrophy (PCA), two neurodegenerative conditions that are associated with progressive parietal atrophy. The present study investigated these number systems in CBS and PCA by assessing the property of the ANS associated with smaller and larger numerosities, and the chunking property of the PIS. The results revealed that CBS/PCA patients are impaired in simple calculations (e.g., addition and subtraction) and that their performance strongly correlates with the size of the numbers involved in these calculations, revealing a clear magnitude effect. This magnitude effect correlated with gray matter atrophy in parietal regions. Moreover, a numeral-dots transcoding task showed that CBS/PCA patients are able to take advantage of clustering in the spatial distribution of the dots of the array. The relative advantage associated with chunking compared to a random spatial distribution correlated with both parietal and prefrontal regions. These results shed light on the properties of systems for representing number knowledge in non-aphasic patients with CBS and PCA. PMID:25278132

Eliminating barriers to personalized medicine: learning from neurofibromatosis type 1.

PubMed

Gutmann, David H

2014-07-29

With the emergence of high-throughput discovery platforms, robust preclinical small-animal models, and efficient clinical trial pipelines, it is becoming possible to envision a time when the treatment of human neurologic diseases will become personalized. The emergence of precision medicine will require the identification of subgroups of patients most likely to respond to specific biologically based therapies. This stratification only becomes possible when the determinants that contribute to disease heterogeneity become more fully elucidated. This review discusses the defining factors that underlie disease heterogeneity relevant to the potential for individualized brain tumor (optic pathway glioma) treatments arising in the common single-gene cancer predisposition syndrome, neurofibromatosis type 1 (NF1). In this regard, NF1 is posited as a model genetic condition to establish a workable paradigm for actualizing precision therapeutics for other neurologic disorders. © 2014 American Academy of Neurology.

Acute coronary syndromes: is there a place for a real pre-hospital treatment for patients "en route" to the coronary intensive care unit?

PubMed

Assez, Nathalie; Smith, Grégoire; Adriansen, Christophe; Aboukais, Wissam; Wiel, Eric; Goldstein, Patrick

2012-08-01

Acute initial management of patients with acute coronary syndrome (ACS) is based on a precise clinical and electrocardiographic diagnosis. Initial risk stratification in the pre-hospital phase is the key step. The last step, adequate patient routing, is decided based on emergency level and reperfusion strategies, considered right from the pre-hospital phase. The management of a patient with an ACS requires close collaboration between emergency physicians and cardiologists, according to simplified protocols for easier access to catheterisation. The next challenges for the pre-hospital management of ACS are based on: - precise knowledge of new antiplatelet and anticoagulant drugs by the emergency physicians, in order to adjust their prescriptions to the patient profile; - developing co-operation between hospitals, according to regional specificities (geographic considerations and distribution of PCI centres) in order to reduce access time to catheterisation rooms; - organising the healthcare network, where the SAMU has an essential role in coordinating the different medical actors; - regular analysis of the evolution of our professional practices, considering, e.g., the guidelines of the "HAS" (French official healthcare guidelines institute);- integrating pre-hospital medicine in health prevention programmes; - improving our understanding of the population's presentations of coronary artery disease, in order to encourage the patients and their families to call the EMS as soon as possible. The challenge of the emergency physician is to adapt the strategies to the patient's needs.

Immunological aspects of nonimmediate reactions to beta-lactam antibiotics.

PubMed

Rodilla, Esther Morena; González, Ignacio Dávila; Yges, Elena Laffond; Bellido, Francisco Javier Múñoz; Bara, María Teresa Gracia; Toledano, Félix Lorente

2010-09-01

beta-lactam antibiotics are the agents most frequently implied in immune drug adverse reactions. These can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Mechanisms of immediate IgE-mediated reactions are widely studied and are therefore better understood. Nonimmediate reactions include a broad number of clinical entities like mild maculopapular exanthemas, the most common, and other less frequent but more severe reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, acute exanthematic pustulosis or cytopenias. These nonimmediate reactions are mainly mediated by T cells but the precise underlying mechanisms are not well elucidated. This fact complicates the allergological evaluation of patients with this type of reaction and available tests have demonstrated poor sensitivity and specificity.

A Tale of Two Morphs: Modeling Pollen Transfer, Magic Traits, and Reproductive Isolation in Parapatry

PubMed Central

Haller, Benjamin C.; de Vos, Jurriaan M.; Keller, Barbara; Hendry, Andrew P.; Conti, Elena

2014-01-01

The evolution of the flower is commonly thought to have spurred angiosperm diversification. Similarly, particular floral traits might have promoted diversification within specific angiosperm clades. We hypothesize that traits promoting the precise positional transfer of pollen between flowers might promote diversification. In particular, precise pollen transfer might produce partial reproductive isolation that facilitates adaptive divergence between parapatric populations differing in their reproductive-organ positions. We investigate this hypothesis with an individual-based model of pollen transfer dynamics associated with heterostyly, a floral syndrome that depends on precise pollen transfer. Our model shows that precise pollen transfer can cause sexual selection leading to divergence in reproductive-organ positions between populations served by different pollinators, pleiotropically causing an increase in reproductive isolation through a “magic trait” mechanism. Furthermore, this increased reproductive isolation facilitates adaptive divergence between the populations in an unlinked, ecologically selected trait. In a different pollination scenario, however, precise pollen transfer causes a decrease in adaptive divergence by promoting asymmetric gene flow. Our results highlight the idea that magic traits are not “magic” in isolation; in particular, the effect size of magic traits in speciation depends on the external environment, and also on other traits that modify the strength of the magic trait's influence on non-random mating. Overall, we show that the evolutionary consequences of pollen transfer dynamics can depend strongly on the available pollinator fauna and on the morphological fit between flowers and pollinators. Furthermore, our results illustrate the potential importance of even weak reproductive isolating barriers in facilitating adaptive divergence. PMID:25211280

A tale of two morphs: modeling pollen transfer, magic traits, and reproductive isolation in parapatry.

PubMed

Haller, Benjamin C; de Vos, Jurriaan M; Keller, Barbara; Hendry, Andrew P; Conti, Elena

2014-01-01

The evolution of the flower is commonly thought to have spurred angiosperm diversification. Similarly, particular floral traits might have promoted diversification within specific angiosperm clades. We hypothesize that traits promoting the precise positional transfer of pollen between flowers might promote diversification. In particular, precise pollen transfer might produce partial reproductive isolation that facilitates adaptive divergence between parapatric populations differing in their reproductive-organ positions. We investigate this hypothesis with an individual-based model of pollen transfer dynamics associated with heterostyly, a floral syndrome that depends on precise pollen transfer. Our model shows that precise pollen transfer can cause sexual selection leading to divergence in reproductive-organ positions between populations served by different pollinators, pleiotropically causing an increase in reproductive isolation through a "magic trait" mechanism. Furthermore, this increased reproductive isolation facilitates adaptive divergence between the populations in an unlinked, ecologically selected trait. In a different pollination scenario, however, precise pollen transfer causes a decrease in adaptive divergence by promoting asymmetric gene flow. Our results highlight the idea that magic traits are not "magic" in isolation; in particular, the effect size of magic traits in speciation depends on the external environment, and also on other traits that modify the strength of the magic trait's influence on non-random mating. Overall, we show that the evolutionary consequences of pollen transfer dynamics can depend strongly on the available pollinator fauna and on the morphological fit between flowers and pollinators. Furthermore, our results illustrate the potential importance of even weak reproductive isolating barriers in facilitating adaptive divergence.

Morphologic analysis of artifacts in human fetal eyes confounding histopathologic investigations.

PubMed

Herwig, Martina C; Müller, Annette M; Holz, Frank G; Loeffler, Karin U

2011-04-25

Human fetal eyes are an excellent source for studies of the normal ocular development and for examining early ocular changes associated with various syndromes in the context of a pediatric pathologic or prenatal sonographic diagnosis. However, artifacts caused by different factors often render an exact interpretation difficult. In this study, the frequency and extent of artifacts in human fetal eyes were investigated with the aim of distinguishing more precisely these artifacts from real findings, allowing also for a more diligent forensic interpretation. The cohort included 341 fetal eyes, ranging in age from 8 to 38 weeks of gestation, that were investigated macroscopically and by light microscopy. In most specimens, artifacts such as pigment spillage and autolytic changes of the retina were noted. Nearly all specimens showed changes of the lens with remarkable similarities to cataractous lenses in adult eyes. Structural ocular changes associated with systemic syndromes were also observed and in most instances could be distinguished from artifacts. Morphologic changes in fetal eyes should be classified in artifacts caused by way of abortion, mechanical effects from the removal of the eyes, delayed fixation with autolysis, and the fixative itself and should be distinguished from genuine structural abnormalities associated with ocular or systemic disease. This classification can be fairly difficult and requires experience. In addition, lens artifacts are often misleading, and the diagnosis of a fetal cataract should not be made based on histopathologic examination alone.

Leveraging premalignant biology for immune-based cancer prevention.

PubMed

Spira, Avrum; Disis, Mary L; Schiller, John T; Vilar, Eduardo; Rebbeck, Timothy R; Bejar, Rafael; Ideker, Trey; Arts, Janine; Yurgelun, Matthew B; Mesirov, Jill P; Rao, Anjana; Garber, Judy; Jaffee, Elizabeth M; Lippman, Scott M

2016-09-27

Prevention is an essential component of cancer eradication. Next-generation sequencing of cancer genomes and epigenomes has defined large numbers of driver mutations and molecular subgroups, leading to therapeutic advances. By comparison, there is a relative paucity of such knowledge in premalignant neoplasia, which inherently limits the potential to develop precision prevention strategies. Studies on the interplay between germ-line and somatic events have elucidated genetic processes underlying premalignant progression and preventive targets. Emerging data hint at the immune system's ability to intercept premalignancy and prevent cancer. Genetically engineered mouse models have identified mechanisms by which genetic drivers and other somatic alterations recruit inflammatory cells and induce changes in normal cells to create and interact with the premalignant tumor microenvironment to promote oncogenesis and immune evasion. These studies are currently limited to only a few lesion types and patients. In this Perspective, we advocate a large-scale collaborative effort to systematically map the biology of premalignancy and the surrounding cellular response. By bringing together scientists from diverse disciplines (e.g., biochemistry, omics, and computational biology; microbiology, immunology, and medical genetics; engineering, imaging, and synthetic chemistry; and implementation science), we can drive a concerted effort focused on cancer vaccines to reprogram the immune response to prevent, detect, and reject premalignancy. Lynch syndrome, clonal hematopoiesis, and cervical intraepithelial neoplasia which also serve as models for inherited syndromes, blood, and viral premalignancies, are ideal scenarios in which to launch this initiative.

Effects of Probiotics and Synbiotics on Obesity, Insulin Resistance Syndrome, Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease: A Review of Human Clinical Trials.

PubMed

Sáez-Lara, Maria Jose; Robles-Sanchez, Candido; Ruiz-Ojeda, Francisco Javier; Plaza-Diaz, Julio; Gil, Angel

2016-06-13

The use of probiotics and synbiotics in the prevention and treatment of different disorders has dramatically increased over the last decade. Both probiotics and synbiotics are well known ingredients of functional foods and nutraceuticals and may provide beneficial health effects because they can influence the intestinal microbial ecology and immunity. The present study reviews the effects of probiotics and synbiotics on obesity, insulin resistance syndrome (IRS), type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) in human randomized clinical trials. Select probiotics and synbiotics provided beneficial effects in patients with obesity, mainly affecting the body mass index and fat mass. Some probiotics had beneficial effects on IRS, decreasing the cell adhesion molecule-1 levels, and the synbiotics decreased the insulin resistance and plasma lipid levels. Moreover, select probiotics improved the carbohydrate metabolism, fasting blood glucose, insulin sensitivity and antioxidant status and also reduced metabolic stress in subjects with T2D. Some probiotics and synbiotics improved the liver and metabolic parameters in patients with NAFLD. The oral intake of probiotics and synbiotics as co-adjuvants for the prevention and treatment of obesity, IRS, T2D and NAFLD is partially supported by the data shown in the present review. However, further studies are required to understand the precise mechanism of how probiotics and synbiotics affect these metabolic disorders.

Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management

PubMed Central

Blasco-Algora, Sara; Masegosa-Ataz, José; Gutiérrez-García, María Luisa; Alonso-López, Sonia; Fernández-Rodríguez, Conrado M

2015-01-01

Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies. PMID:26576097

Genetic variation in insulin-induced kinase signaling

PubMed Central

Wang, Isabel Xiaorong; Ramrattan, Girish; Cheung, Vivian G

2015-01-01

Individual differences in sensitivity to insulin contribute to disease susceptibility including diabetes and metabolic syndrome. Cellular responses to insulin are well studied. However, which steps in these response pathways differ across individuals remains largely unknown. Such knowledge is needed to guide more precise therapeutic interventions. Here, we studied insulin response and found extensive individual variation in the activation of key signaling factors, including ERK whose induction differs by more than 20-fold among our subjects. This variation in kinase activity is propagated to differences in downstream gene expression response to insulin. By genetic analysis, we identified cis-acting DNA variants that influence signaling response, which in turn affects downstream changes in gene expression and cellular phenotypes, such as protein translation and cell proliferation. These findings show that polymorphic differences in signal transduction contribute to individual variation in insulin response, and suggest kinase modulators as promising therapeutics for diseases characterized by insulin resistance. PMID:26202599

Privacy protection versus cluster detection in spatial epidemiology.

PubMed

Olson, Karen L; Grannis, Shaun J; Mandl, Kenneth D

2006-11-01

Patient data that includes precise locations can reveal patients' identities, whereas data aggregated into administrative regions may preserve privacy and confidentiality. We investigated the effect of varying degrees of address precision (exact latitude and longitude vs the center points of zip code or census tracts) on detection of spatial clusters of cases. We simulated disease outbreaks by adding supplementary spatially clustered emergency department visits to authentic hospital emergency department syndromic surveillance data. We identified clusters with a spatial scan statistic and evaluated detection rate and accuracy. More clusters were identified, and clusters were more accurately detected, when exact locations were used. That is, these clusters contained at least half of the simulated points and involved few additional emergency department visits. These results were especially apparent when the synthetic clustered points crossed administrative boundaries and fell into multiple zip code or census tracts. The spatial cluster detection algorithm performed better when addresses were analyzed as exact locations than when they were analyzed as center points of zip code or census tracts, particularly when the clustered points crossed administrative boundaries. Use of precise addresses offers improved performance, but this practice must be weighed against privacy concerns in the establishment of public health data exchange policies.

Lordosis manoeuvre in the diagnosis of lumbar facet syndrome.

PubMed

Díez-Ulloa, M A; Almira Suárez, E L; Otero Fernández, M; Leborans Eiras, S; Collado Arce, G

2016-01-01

In lumbar pain patients an aetiopathogenic diagnosis leads to a better management. When there are alarm signs, they should be classified on an anatomical basis through anamnesis and physical examination. A significant group is of facet origin (lumbar facet syndrome [LFS]), but the precise clinical diagnosis remains cumbersome and time-consuming. In clinical practice it is observed that patients with an advanced degenerative disease do not perform extension or rotation of their lumbar spine when prompted to extend it, but rather knee flexion, making the manoeuvre meaningless. For this reason, a new simple and quick clinical test was developed for the diagnosis of lumbar facet syndrome, with a facet block-test as a confirmation. The new test is better than a classic one in the diagnosis of facet syndrome, and probably even better than imaging studies A prospective study was conducted on a series of 68 patients (01/01/2012-30/06/2013). A comparison in between: classic manoeuvre (CM), imaging diagnostics (ID), and the new lordosis manoeuvre (LM) test. Examination and block test by one author, and evaluation of results by another one. Deformity and instability. using a physical. To determine the effectiveness of a new clinical test (LM) for the diagnosis of LFS (as confirmed by a positive block-test of medial branch of dorsal ramus of the lumbar root, RMRDRL). R package software. The LM was most effective (p<.0001; Kappa 0.524, p<.001). There was no correlation between either the CM or ID and the block-test results (Kappa, CM: 0.078; p=.487, and ID: 0.195; p=.105). There was a correlation between ID (CAT/MR) and LM (p=.024; Kappa 0.289 p=.014), although not with CM. There was no correlation between ID (plain X-rays) and CM or LM. A new test for diagnosis of LFS is presented that is reliable, quick, and simple. Clinical examination is more reliable than imaging test for the diagnosis of LFS. Copyright © 2016 SECOT. Published by Elsevier Espana. All rights reserved.

Clinicopathologic implications of DNA mismatch repair status in endometrial carcinomas.

PubMed

Shikama, Ayumi; Minaguchi, Takeo; Matsumoto, Koji; Akiyama-Abe, Azusa; Nakamura, Yuko; Michikami, Hiroo; Nakao, Sari; Sakurai, Manabu; Ochi, Hiroyuki; Onuki, Mamiko; Satoh, Toyomi; Oki, Akinori; Yoshikawa, Hiroyuki

2016-02-01

Endometrial carcinoma is the most common malignancy in women with Lynch syndrome caused by mismatch repair (MMR) deficiency. We investigated the clinicopathologic significance of deficient MMR and Lynch syndrome presumed by MMR analyses in unselected endometrial carcinomas. We analyzed immunohistochemistry of MMR proteins (MLH1/MSH2/MSH6/PMS2) and MLH1 promoter methylation in primary endometrial carcinomas from 221 consecutive patients. Based on these results, tumors were categorized as sporadic or probable Lynch syndrome (PLS). Clinicopathologic variables and prognosis were compared according to MMR status and sporadic/PLS classification. Deficient MMR showed only trends towards favorable overall survival (OS) compared with intact MMR (p=0.13), whereas PLS showed significantly better OS than sporadic (p=0.038). Sporadic was significantly associated with older age, obesity, deep myometrial invasion, and advanced stage (p=0.008, 0.01, 0.02 and 0.03), while PLS was significantly associated with early stage and Lynch syndrome-associated multiple cancer (p=0.04 and 0.001). The trend towards favorable OS of PLS was stronger in advanced stage than in early stage (hazard ratio, 0.044 [95% CI 0-25.6] vs. 0.49 [0.063-3.8]). In the subset receiving adjuvant therapies, PLS showed trends towards favorable disease-free survival compared to sporadic by contrast with patients receiving no adjuvant therapies showing no such trend (hazard ratio, 0.045 [95% CI 0-20.3] vs. 0.81 [0.095-7.0]). The current findings suggest that analyzing MMR status and searching for Lynch syndrome may identify a subset of patients with favorable survival and high sensitivity to adjuvant therapies, providing novel and useful implications for formulating the precision medicine in endometrial carcinoma. Copyright © 2015 Elsevier Inc. All rights reserved.

[Simultaneous determination of guanidinoacetate, creatine and creatinine by liquid chromatography-tandem mass spectrometry: a diagnostic tool for creatine deficiency syndromes in body fluids and a perspective use on cultured fibroblasts].

PubMed

Van Noolen, Laetitia; Monneret, Denis; Ducros, Véronique; Corne, Christelle; Lunardi, Joël; Faure, Patrice

2013-01-01

Guanidinoacetate (GAA) and creatine (Cr) are creatine deficiency syndromes (CDS) biochemical markers. We describe a liquid chromatography - tandem mass spectrometry method (LC/MSMS) performing simultaneous analysis of GAA, Cr and creatinine (Crn). Study of Cr uptake by fibroblasts for Cr transporter defect diagnosis is also assessed. The three butylated compounds were separated by liquid chromatography and MSMS quantification was achieved by isotopic dilution with electrospray positive ion mode. Linearity was demonstrated from 0 to 600, 675 and 4500 μmol/L and limit of quantification was 0.1, 0.04 and 0.9 μmol/L for GAA, Cr, and Crn respectively. Intra- and inter-assay precision for each analyte was better than 11%, and standard recoveries ranged from 83 to 109%. Reference values in cerebrospinal fluid samples for subjects ≥14 years were also established for GAA and Cr. Five fibroblast cell lines were used for Cr uptake study. Cr uptake by fibroblasts increased with the Cr media concentrations and was significantly inhibited by 3-guanidinopropionate (500 μmol/L), a Cr transporter inhibitor (96h incubation, [Cr media] = 25 μmol/L, p<0.05). A reliable LC/MSMS method for the diagnosis of CDS was developed in different biological fluids. Finally, results of the Cr uptake study reinforce the interest of this technique to diagnose Cr transporter deficiencies.

Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in the Treatment of Obese Women with Polycystic Ovary Syndrome.

PubMed

Tzotzas, Themistoklis; Karras, Spyridon N; Katsiki, Niki

2017-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in females and is often associated with a number of cardiometabolic disorders such as central obesity, dyslipidaemia, hypertension, insulin resistance, hyperinsulinaemia, glucose intolerance and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 (GLP-1), a gut hormone secreted after a meal, enhances glucosestimulated insulin secretion and additionally suppresses appetite and gastric motility. Most studies found impaired GLP-1 kinetics in obese individuals, whereas small studies in PCOS reported reduced, normal or even elevated GLP-1 levels. Apart from their efficacy in patients with T2DM, some GLP-1 receptor agonists (GLP-1 RAs) have been successfully tested in terms of both efficiency and safety in obese individuals without diabetes and liraglutide 3 mg once daily has been approved as an antiobesity drug in the USA and the European Union. Recently, some small trials of short duration using GLP-1 RAs as monotherapy or combined with metformin in obese PCOS women showed positive results regarding weight reduction and a decrease in testosterone levels but without significant effects on insulin levels, insulin sensitivity and menstrual patterns. Longer term studies with more patients and higher doses of liraglutide (as this drug is already approved for obese individuals) are required to determine the precise indications of GLP-1 RAs in PCOS and to evaluate safety issues. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis: a multicenter retrospective study of 377 adult patients from the United States.

PubMed

Micheletti, Robert G; Chiesa-Fuxench, Zelma; Noe, Megan H; Stephen, Sasha; Aleshin, Maria; Agarwal, Ashwin; Boggs, Jennifer; Cardones, Adela R; Chen, Jennifer K; Cotliar, Jonathan; Davis, Mark Dp; Dominguez, Arturo; Fox, Lindy P; Gordon, Shayna; Hamrick, Ronald; Ho, Baran; Hughey, Lauren C; Jones, Larry M; Kaffenberger, Benjamin H; Kindley, Kimball; Kroshinsky, Daniela; Kwong, Bernice Y; Miller, Daniel D; Mostaghimi, Arash; Musiek, Amy; Ortega-Loayza, Alex G; Patel, Raj; Posligua, Alba; Rani, Monica; Saluja, Sandeep; Sharon, Victoria R; Shinkai, Kanade; John, Jessica St; Strickland, Nicole; Summers, Erika M; Sun, Natalie; Wanat, Karolyn A; Wetter, David A; Worswick, Scott; Yang, Caroline; Margolis, David J; Gelfand, Joel M; Rosenbach, Misha

2018-05-11

Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) is a rare, severe mucocutaneous reaction with few large cohorts reported. This multicenter retrospective study included patients with SJS/TEN seen by inpatient consultative dermatologists at 18 academic medical centers in the United States. 377 adult patients with SJS/TEN between 1/1/2000 and 6/1/2015 were entered, including 69.0% from 2010 onward. The most frequent cause of SJS/TEN was medication reaction (89.7%), most often trimethoprim / sulfamethoxazole (27.2%). The majority of patients were managed in an intensive care (27.2%) or burn unit (41.0%). Most received pharmacologic therapy (70.7%) versus supportive care alone (29.3%)-typically corticosteroids (42.5%), IVIG (35.3%), or both therapies (20.3%). Based on Day 1 SCORTEN predicted mortality, 78 in-hospital deaths were expected (21%), while the observed mortality of 54 patients (14.7%) was significantly lower (SMR 0.70; CI 0.58, 0.79). Stratified by therapy received, the standardized mortality ratio was lowest among those receiving both steroids and IVIG (0.52; CI 0.21, 0.79). This large cohort provides contemporary information regarding US patients with SJS/TEN. Mortality, while substantial, was significantly lower than predicted. While the precise role of pharmacotherapy remains unclear, co-administration of corticosteroids and IVIG, among other therapies, may warrant further study. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Novel USH2A mutations in Japanese Usher syndrome type 2 patients: marked differences in the mutation spectrum between the Japanese and other populations.

PubMed

Nakanishi, Hiroshi; Ohtsubo, Masafumi; Iwasaki, Satoshi; Hotta, Yoshihiro; Usami, Shin-Ichi; Mizuta, Kunihiro; Mineta, Hiroyuki; Minoshima, Shinsei

2011-07-01

Usher syndrome (USH) is an autosomal recessive disorder characterized by retinitis pigmentosa and hearing loss. USH type 2 (USH2) is the most common type of USH and is frequently caused by mutations in USH2A. In a recent mutation screening of USH2A in Japanese USH2 patients, we identified 11 novel mutations in 10 patients and found the possible frequent mutation c.8559-2A>G in 4 of 10 patients. To obtain a more precise mutation spectrum, we analyzed further nine Japanese patients in this study. We identified nine mutations, of which eight were novel. This result indicates that the mutation spectrum for USH2A among Japanese patients largely differs from Caucasian, Jewish and Palestinian patients. Meanwhile, we did not find the c.8559-2A>G in this study. Haplotype analysis of the c.8559-2G (mutated) alleles using 23 single nucleotide polymorphisms surrounding the mutation revealed an identical haplotype pattern of at least 635 kb in length, strongly suggesting that the mutation originated from a common ancestor. The fact that all patients carrying c.8559-2A>G came from western Japan suggests that the mutation is mainly distributed in that area; indeed, most of the patients involved in this study came from eastern Japan, which contributed to the absence of c.8559-2A>G.

Radiofrequency volumetric reduction of the tongue. A porcine pilot study for the treatment of obstructive sleep apnea syndrome.

PubMed

Powell, N B; Riley, R W; Troell, R J; Blumen, M B; Guilleminault, C

1997-05-01

To investigate, in an animal model, the feasibility of radiofrequency (RF) volumetric tongue reduction for the future purpose of determining its clinical applications in obstructive sleep apnea syndrome (OSAS). The study was performed in three stages, one in vitro bovine stage and two in vivo porcine stages. The last stage was a prospective investigation with histologic and volumetric analyses to establish outcomes. Laboratory and operating room of veterinary research center. A homogeneous population of porcine animal models, including seven in stage 2 and 12 in stage 3. RF energy was delivered by a custom-fabricated needle electrode and RF generator to the tongue tissue of both the in vitro and in vivo models. Microultransonic crystals were used to measure three-dimensional changes (volumetric reduction). Lesion size correlated well with increasing RF energy delivery (Sperman correlation coefficient of 0.986; p = 0.0003). Histologic assessments done serially over time (1 h through 3 weeks) showed a well-circumscribed lesion with a normal healing progression and no peripheral damage to nerves. Volumetric analysis documented a very mild initial edematous response that promptly tapered at 24 h. At 10 days after RF, a 26.3% volume reduction was documented at the treatment site (circumscribed by the microultrasonic crystals). RF, in a porcine animal model, can safely reduce tongue volume in a precise and controlled manner. Further studies will validate the use of RF in the treatment of OSAS.

Eagle syndrome surgical treatment with piezosurgery.

PubMed

Bertossi, Dario; Albanese, Massimo; Chiarini, Luigi; Corega, Claudia; Mortellaro, Carmen; Nocini, Pierfrancesco

2014-05-01

Eagle syndrome (ES) is an uncommon complication of styloid process elongation with stylohyoideal complex symptomatic calcification. It is an uncommon condition (4% of the population) that is symptomatic in only 4% of the cases. Eagle syndrome is usually an acquired condition that can be related to tonsillectomy or to a neck trauma. A type of ES is the styloid-carotid syndrome, a consequence of the irritation of pericarotid sympathetic fibers and compression on the carotid artery. Clinical manifestations are found most frequently after head turning and neck compression. Although conservative treatment (analgesics, anticonvulsants, antidepressants, local infiltration with steroids, or anesthetic agents) have been used, surgical treatment is often the only effective treatment in symptomatic cases. We present the case of a 55-year-old patient, successfully treated under endotracheal anesthesia. The cranial portion of the calcified styloid process was shortened through an external approach, using a piezoelectric cutting device (Piezosurgery Medical II; Mectron Medical Technology, Carasco, Italy) with MT1-10 insert, pump level 4, vibration level 7. No major postoperative complications such as nerve damage, hematoma, or wound dehiscence occurred. After 6 months, the patient was completely recovered. Two years after the surgery, the patient did not refer any symptoms related to ES. The transcervical surgical approach in patients with ES seems to be safe and effective, despite the remarkable risk for transient marginal mandibular nerve palsy. This risk can be decreased by the use of the piezoelectric device for its distinctive characteristics--such as precision, selective cut action, and bloodless cut.

Does Experience of Failure Decrease Executive, Regulatory Abilities and Increase Aggression?

PubMed Central

Pahlavan, Farzaneh; Mouchiroud, Christophe; Nemlaghi-Manis, Emna

2012-01-01

Recent advances in the study of affective-cognitive regulation of aggressive behavior suggest positive correlations between poor executive capacities (ECF) and dispositional negative reactivity (Posner & Rothbart, 2000). If the global assumption is correct what are the likely implications of predicted relation? The central issue in present research was to verify this assumption and examine how situational characteristics could alter executive performance in persons with Dysexecutive Syndrome (DES, Baddeley, 1998) and healthy adults (students, health workers) to explore some of the consequences of those modifications for aggressive tendencies. Precisely, we expected the positive correlations between poor executive performances and high aggressive tendencies at dispositional as well situational levels, except for health workers, given their professional duties. In order to assess cognitive capacities and dispositional as well as situational aggressive tendencies, during two studies (First study: N=60 students; Second study: N= 60 students, N= 24 patient with Dysexecutive Syndrome, N= 45 health care workers) right-handed French-speakers participants completed twice, during an initial phase of the study and one week after, a series of standard executive functions neuropsychological tests and aggression questionnaires. During second phase, participants executed a task introducing the experimental feedbacks (success, neutral, failure) before completion of neuropsychological tests and questionnaires. The results provided evidence of a dispositional relationship between poor executive functioning and aggressive tendencies, and extended it to situational level. For all participants, it showed that increases in impulsiveness (negative emotionality and aggressive choices) due to a negative feedback were concomitant with an inability to focus individuals’ attention on ongoing tasks. PMID:23121744

Thoracoscopic splanchnicectomy as a palliative procedure for pain relief in carcinoma pancreas.

PubMed

Prasad, Arun; Choudhry, Piush; Kaul, Sunil; Srivastava, Gaurav; Ali, Mudasir

2009-04-01

Thoracoscopic splanchnicectomy has been used for the management of upper abdominal pain syndromes as an alternative to celiac plexus block for conditions such as chronic pancreatitis or supramesocolic malignant neoplasms, including unresectable pancreatic cancer. This procedure is similar to the percutaneous block with a higher degree of precision and avoids the side effects associated with the local diffusion of neurolytic solutions. Thoracoscopic splanchnicectomy appears to be a better treatment in such cases as the procedure is done under direct vision and less dependent on anatomical variations.

Thoracoscopic splanchnicectomy as a palliative procedure for pain relief in carcinoma pancreas

PubMed Central

Prasad, Arun; Choudhry, Piush; Kaul, Sunil; Srivastava, Gaurav; Ali, Mudasir

2009-01-01

Thoracoscopic splanchnicectomy has been used for the management of upper abdominal pain syndromes as an alternative to celiac plexus block for conditions such as chronic pancreatitis or supramesocolic malignant neoplasms, including unresectable pancreatic cancer. This procedure is similar to the percutaneous block with a higher degree of precision and avoids the side effects associated with the local diffusion of neurolytic solutions. Thoracoscopic splanchnicectomy appears to be a better treatment in such cases as the procedure is done under direct vision and less dependent on anatomical variations. PMID:19727377

[Nihilodermia in psychodermatology].

PubMed

Harth, W; Hermes, B; Seikowski, K; Gieler, U

2007-05-01

"Nihilodermia" refers to a group of difficult "problem" patients in dermatology without objective findings but with recurrent symptoms and stubborn demand for medical examination. These primary emotional disorders are somatoform disorders, but the patients usually strictly deny a psychosocial aspect and expect purely somatic treatment. Clinical patterns include pruritus, pain, paresthesias, feelings of disfiguration, eco-syndromes, erythrophobia and psychogenic pseudoeffluvium. The relevant somatoform disorders in dermatology can be differentiated as somatization disorders, hypochondriacal disorders, somatoform autonomous disorders, persistent somatoform pain disorders and "other somatoform disorders". A precise differential diagnostic division is necessary in order to initiate adequate therapy strategies.

Mutations in SMG9, Encoding an Essential Component of Nonsense-Mediated Decay Machinery, Cause a Multiple Congenital Anomaly Syndrome in Humans and Mice

PubMed Central

Shaheen, Ranad; Anazi, Shams; Ben-Omran, Tawfeg; Seidahmed, Mohammed Zain; Caddle, L. Brianna; Palmer, Kristina; Ali, Rehab; Alshidi, Tarfa; Hagos, Samya; Goodwin, Leslie; Hashem, Mais; Wakil, Salma M.; Abouelhoda, Mohamed; Colak, Dilek; Murray, Stephen A.; Alkuraya, Fowzan S.

2016-01-01

Nonsense-mediated decay (NMD) is an important process that is best known for degrading transcripts that contain premature stop codons (PTCs) to mitigate their potentially harmful consequences, although its regulatory role encompasses other classes of transcripts as well. Despite the critical role of NMD at the cellular level, our knowledge about the consequences of deficiency of its components at the organismal level is largely limited to model organisms. In this study, we report two consanguineous families in which a similar pattern of congenital anomalies was found to be most likely caused by homozygous loss-of-function mutations in SMG9, encoding an essential component of the SURF complex that generates phospho-UPF1, the single most important step in NMD. By knocking out Smg9 in mice via CRISPR/Cas9, we were able to recapitulate the major features of the SMG9-related multiple congenital anomaly syndrome we observed in humans. Surprisingly, human cells devoid of SMG9 do not appear to have reduction of PTC-containing transcripts but do display global transcriptional dysregulation. We conclude that SMG9 is required for normal human and murine development, most likely through a transcriptional regulatory role, the precise nature of which remains to be determined. PMID:27018474

Fundus Autofluorescence Imaging of the White Dot Syndromes

PubMed Central

Yeh, Steven; Forooghian, Farzin; Wong, Wai T.; Faia, Lisa J.; Cukras, Catherine; Lew, Julie C.; Wroblewski, Keith; Weichel, Eric D.; Meyerle, Catherine B.; Sen, Hatice Nida; Chew, Emily Y.; Nussenblatt, Robert B.

2011-01-01

Objective To characterize the fundus autofluorescence (FAF) findings in patients with white dot syndromes (WDSs). Methods Patients with WDSs underwent ophthalmic examination, fundus photography, fluorescein angiography, and FAF imaging. Patients were categorized as having no, minimal, or predominant foveal hypoautofluorescence. The severity of visual impairment was then correlated with the degree of foveal hypoautofluorescence. Results Fifty-five eyes of 28 patients with WDSs were evaluated. Visual acuities ranged from 20/12.5 to hand motions. Diagnoses included serpiginous choroidopathy (5 patients), birdshot retinochoroidopathy (10), multifocal choroiditis (8), relentless placoid chorioretinitis (1), presumed tuberculosis-associated serpiginouslike choroidopathy (1), acute posterior multifocal placoid pigment epitheliopathy (1), and acute zonal occult outer retinopathy (2). In active serpiginous choroidopathy, notable hyperautofluorescence in active disease distinguished it from the variegated FAF features of tuberculosis-associated serpiginouslike choroidopathy. The percentage of patients with visual acuity impairment of less than 20/40 differed among eyes with no, minimal, and predominant foveal hypoautofluorescence (P<.001). Patients with predominant foveal hypoautofluorescence demonstrated worse visual acuity than those with minimal or no foveal hypoautofluorescence (both P<.001). Conclusions Fundus autofluorescence imaging is useful in the evaluation of the WDS. Visual acuity impairment is correlated with foveal hypoautofluorescence. Further studies are needed to evaluate the precise role of FAF imaging in the WDSs. PMID:20065216

Fundus autofluorescence imaging of the white dot syndromes.

PubMed

Yeh, Steven; Forooghian, Farzin; Wong, Wai T; Faia, Lisa J; Cukras, Catherine; Lew, Julie C; Wroblewski, Keith; Weichel, Eric D; Meyerle, Catherine B; Sen, Hatice Nida; Chew, Emily Y; Nussenblatt, Robert B

2010-01-01

To characterize the fundus autofluorescence (FAF) findings in patients with white dot syndromes (WDSs). Patients with WDSs underwent ophthalmic examination, fundus photography, fluorescein angiography, and FAF imaging. Patients were categorized as having no, minimal, or predominant foveal hypoautofluorescence. The severity of visual impairment was then correlated with the degree of foveal hypoautofluorescence. Fifty-five eyes of 28 patients with WDSs were evaluated. Visual acuities ranged from 20/12.5 to hand motions. Diagnoses included serpiginous choroidopathy (5 patients), birdshot retinochoroidopathy (10), multifocal choroiditis (8), relentless placoid chorioretinitis (1), presumed tuberculosis-associated serpiginouslike choroidopathy (1), acute posterior multifocal placoid pigment epitheliopathy (1), and acute zonal occult outer retinopathy (2). In active serpiginous choroidopathy, notable hyperautofluorescence in active disease distinguished it from the variegated FAF features of tuberculosis-associated serpiginouslike choroidopathy. The percentage of patients with visual acuity impairment of less than 20/40 differed among eyes with no, minimal, and predominant foveal hypoautofluorescence (P < .001). Patients with predominant foveal hypoautofluorescence demonstrated worse visual acuity than those with minimal or no foveal hypoautofluorescence (both P < .001). Fundus autofluorescence imaging is useful in the evaluation of the WDS. Visual acuity impairment is correlated with foveal hypoautofluorescence. Further studies are needed to evaluate the precise role of FAF imaging in the WDSs.

Precision medicine approaches may be the future for CRLF2 rearranged Down Syndrome Acute Lymphoblastic Leukaemia patients.

PubMed

Page, Elyse C; Heatley, Susan L; Yeung, David T; Thomas, Paul Q; White, Deborah L

2018-06-04

Breakthrough studies over the past decade have uncovered unique gene fusions implicated in acute lymphoblastic leukaemia (ALL). The critical gene, cytokine receptor-like factor 2 (CRLF2), is rearranged in 5-16% of B-ALL, comprising 50% of Philadelphia-like ALL and cooperates with genomic lesions in the Jak, Mapk and Ras signalling pathways. Children with Down Syndrome (DS) have a predisposition to developing CRLF2 rearranged-ALL which is observed in 60% of DS-ALL patients. These patients experience a poor survival outcome. Mutations of genes involved in epigenetic regulation are more prevalent in DS-ALL patients than non-DS ALL patients, highlighting the potential for alternative treatment strategies. DS-ALL patients also suffer greater treatment-related toxicity from current ALL treatment regimens compared to non-DS-ALL patients. An increased gene dosage of critical genes on chromosome 21 which have roles in purine synthesis and folate transport may contribute. As the genomic landscape of DS-ALL patients is different to non-DS-ALL patients, targeted therapies for individual lesions may improve outcomes. Therapeutically targeting each rearrangement with targeted or combination therapy that will perturb the transforming signalling pathways will likely improve the poor survival rates of this subset of patients. Copyright © 2018 Elsevier B.V. All rights reserved.

Oligonucleotide-directed mutagenesis screen to identify pathogenic Lynch syndrome-associated MSH2 DNA mismatch repair gene variants

PubMed Central

Houlleberghs, Hellen; Dekker, Marleen; Lantermans, Hildo; Kleinendorst, Roos; Dubbink, Hendrikus Jan; Hofstra, Robert M. W.; Verhoef, Senno; te Riele, Hein

2016-01-01

Single-stranded DNA oligonucleotides can achieve targeted base-pair substitution with modest efficiency but high precision. We show that “oligo targeting” can be used effectively to study missense mutations in DNA mismatch repair (MMR) genes. Inherited inactivating mutations in DNA MMR genes are causative for the cancer predisposition Lynch syndrome (LS). Although overtly deleterious mutations in MMR genes can clearly be ascribed as the cause of LS, the functional implications of missense mutations are often unclear. We developed a genetic screen to determine the pathogenicity of these variants of uncertain significance (VUS), focusing on mutator S homolog 2 (MSH2). VUS were introduced into the endogenous Msh2 gene of mouse embryonic stem cells by oligo targeting. Subsequent selection for MMR-deficient cells using the guanine analog 6-thioguanine allowed the detection of MMR-abrogating VUS. The screen was able to distinguish weak and strong pathogenic variants from polymorphisms and was used to investigate 59 Msh2 VUS. Nineteen of the 59 VUS were identified as pathogenic. Functional assays revealed that 14 of the 19 detected variants fully abrogated MMR activity and that five of the detected variants attenuated MMR activity. Implementation of the screen in clinical practice allows proper counseling of mutation carriers and treatment of their tumors. PMID:26951660

EULAR Sjögren's syndrome disease activity index (ESSDAI): a user guide

PubMed Central

Seror, Raphaèle; Bowman, Simon J; Brito-Zeron, Pilar; Theander, Elke; Bootsma, Hendrika; Tzioufas, Athanasios; Gottenberg, Jacques-Eric; Ramos-Casals, Manel; Dörner, Thomas; Ravaud, Philippe; Vitali, Claudio; Mariette, Xavier

2015-01-01

The EULAR Sjögren's syndrome (SS) disease activity index (ESSDAI) is a systemic disease activity index that was designed to measure disease activity in patients with primary SS. With the growing use of the ESSDAI, some domains appear to be more challenging to rate than others. The ESSDAI is now in use as a gold standard to measure disease activity in clinical studies, and as an outcome measure, even a primary outcome measure, in current randomised clinical trials. Therefore, ensuring an accurate and reproducible rating of each domain, by providing a more detailed definition of each domain, has emerged as an urgent need. The purpose of the present article is to provide a user guide for the ESSDAI. This guide provides definitions and precisions on the rating of each domain. It also includes some minor improvement of the score to integrate advance in knowledge of disease manifestations. This user guide may help clinicians to use the ESSDAI, and increase the reliability of rating and consequently of the ability to detect true changes over time. This better appraisal of ESSDAI items, along with the recent definition of disease activity levels and minimal clinically important change, will improve the assessment of patients with primary SS and facilitate the demonstration of effectiveness of treatment for patients with primary SS. PMID:26509054

The systemic inflammatory response syndrome (SIRS) to identify infected patients in the emergency room.

PubMed

Jaimes, Fabián; Garcés, Jenny; Cuervo, Jorge; Ramírez, Federico; Ramírez, Jorge; Vargas, Andrea; Quintero, Claudia; Ochoa, Jorge; Tandioy, Fabio; Zapata, Láder; Estrada, Juan; Yepes, Maria; Leal, Hiulber

2003-08-01

Evaluation of the usefulness of criteria for systemic inflammatory response syndrome (SIRS) compared with the final diagnosis of infection in patients admitted to the emergency room of two university-based hospitals. Longitudinal cohort study. Hospital Universitario San Vicente de Paul and Hospital General de Medellín, Medellín, Colombia. PATIENTS. Seven hundred thirty-four patients with suspected infection as main diagnosis for admittance into the emergency room. Sensitivity, specificity, predictive values and likelihood ratios (LR) of SIRS criteria at admission were determined using, as gold standards, the diagnosis at the time of discharge based on clinical history and evolution, and microbiological confirmation of infection. SIRS criteria were met by 503 patients (68.5%); the discharge diagnosis of infection was found in 657 (89.4%) and 276 (37%) had microbiological confirmation. SIRS criteria exhibited a sensitivity of 69%, specificity of 35%, positive predictive value (PPV) of 90%, negative predictive value (NPV) of 12% and positive LR of 1.06. There were no differences between the two gold standards. The finding of two or more SIRS criteria was of little usefulness for diagnosis of infection. It is necessary to work with new criteria and probably with biological markers, in order to obtain a simple, precise and operative definition of the sepsis phenomenon.

Reliable Multi-Label Learning via Conformal Predictor and Random Forest for Syndrome Differentiation of Chronic Fatigue in Traditional Chinese Medicine

PubMed Central

Wang, Huazhen; Liu, Xin; Lv, Bing; Yang, Fan; Hong, Yanzhu

2014-01-01

Objective Chronic Fatigue (CF) still remains unclear about its etiology, pathophysiology, nomenclature and diagnostic criteria in the medical community. Traditional Chinese medicine (TCM) adopts a unique diagnostic method, namely ‘bian zheng lun zhi’ or syndrome differentiation, to diagnose the CF with a set of syndrome factors, which can be regarded as the Multi-Label Learning (MLL) problem in the machine learning literature. To obtain an effective and reliable diagnostic tool, we use Conformal Predictor (CP), Random Forest (RF) and Problem Transformation method (PT) for the syndrome differentiation of CF. Methods and Materials In this work, using PT method, CP-RF is extended to handle MLL problem. CP-RF applies RF to measure the confidence level (p-value) of each label being the true label, and then selects multiple labels whose p-values are larger than the pre-defined significance level as the region prediction. In this paper, we compare the proposed CP-RF with typical CP-NBC(Naïve Bayes Classifier), CP-KNN(K-Nearest Neighbors) and ML-KNN on CF dataset, which consists of 736 cases. Specifically, 95 symptoms are used to identify CF, and four syndrome factors are employed in the syndrome differentiation, including ‘spleen deficiency’, ‘heart deficiency’, ‘liver stagnation’ and ‘qi deficiency’. The Results CP-RF demonstrates an outstanding performance beyond CP-NBC, CP-KNN and ML-KNN under the general metrics of subset accuracy, hamming loss, one-error, coverage, ranking loss and average precision. Furthermore, the performance of CP-RF remains steady at the large scale of confidence levels from 80% to 100%, which indicates its robustness to the threshold determination. In addition, the confidence evaluation provided by CP is valid and well-calibrated. Conclusion CP-RF not only offers outstanding performance but also provides valid confidence evaluation for the CF syndrome differentiation. It would be well applicable to TCM practitioners and facilitate the utilities of objective, effective and reliable computer-based diagnosis tool. PMID:24918430

Induced pluripotent stem cell technology: Toward the future of cardiac arrhythmias.

PubMed

Gnecchi, Massimiliano; Stefanello, Manuela; Mura, Manuela

2017-06-15

The development of human induced pluripotent stem cell (iPSC) technology has revitalized the efforts made in the last decade to exploit the potential of human embryonic stem cells (ESCs) for scientific research. In the field of cardiac arrhythmias, the possibility of generating an unlimited amount of patient-specific cardiomyocyte-like cells (iPSC-CMs) has clear advantages compared with the use of ESC-derived cardiac cells. In particular, with the introduction and implementation of the large-scale precision medicine initiative, we anticipate that the iPSC technology will play an important role in the advancement of cardiovascular research and medicine. This platform is not free from technical limitations that must be carefully taken into account; however, the utility of iPSC-CMs in disease modeling and drug testing studies is hardly questionable. Here, we summarize some of the progresses made in the field of iPSC technology applied to inherited cardiac arrhythmias, with particular emphasis on the use of iPSC-CMs for modelling the long QT syndrome and for the development of personalized drug and molecular therapies. The growing role of iPSC technology in the practice of precision medicine will also be discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

Automated brain volumetrics in multiple sclerosis: a step closer to clinical application

PubMed Central

Beadnall, H N; Hatton, S N; Bader, G; Tomic, D; Silva, D G

2016-01-01

Background Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. Methods MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. Results Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. Conclusions In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies. PMID:27071647

Pituitary Medicine From Discovery to Patient-Focused Outcomes

PubMed Central

2016-01-01

Context: This perspective traces a pipeline of discovery in pituitary medicine over the past 75 years. Objective: To place in context past advances and predict future changes in understanding pituitary pathophysiology and clinical care. Design: Author's perspective on reports of pituitary advances in the published literature. Setting: Clinical and translational Endocrinology. Outcomes: Discovery of the hypothalamic-pituitary axis and mechanisms for pituitary control, have culminated in exquisite understanding of anterior pituitary cell function and dysfunction. Challenges facing the discipline include fundamental understanding of pituitary adenoma pathogenesis leading to more effective treatments of inexorably growing and debilitating hormone secreting pituitary tumors as well as medical management of non-secreting pituitary adenomas. Newly emerging pituitary syndromes include those associated with immune-targeted cancer therapies and head trauma. Conclusions: Novel diagnostic techniques including imaging genomic, proteomic, and biochemical analyses will yield further knowledge to enable diagnosis of heretofore cryptic syndromes, as well as sub classifications of pituitary syndromes for personalized treatment approaches. Cost effective personalized approaches to precision therapy must demonstrate value, and will be empowered by multidisciplinary approaches to integrating complex subcellular information to identify therapeutic targets for enabling maximal outcomes. These goals will be challenging to attain given the rarity of pituitary disorders and the difficulty in conducting appropriately powered prospective trials. PMID:26908107

A partial loss of function allele of Methyl-CpG-binding protein 2 predicts a human neurodevelopmental syndrome

PubMed Central

Samaco, Rodney C.; Fryer, John D.; Ren, Jun; Fyffe, Sharyl; Chao, Hsiao-Tuan; Sun, Yaling; Greer, John J.; Zoghbi, Huda Y.; Neul, Jeffrey L.

2008-01-01

Rett Syndrome, an X-linked dominant neurodevelopmental disorder characterized by regression of language and hand use, is primarily caused by mutations in methyl-CpG-binding protein 2 (MECP2). Loss of function mutations in MECP2 are also found in other neurodevelopmental disorders such as autism, Angelman-like syndrome and non-specific mental retardation. Furthermore, duplication of the MECP2 genomic region results in mental retardation with speech and social problems. The common features of human neurodevelopmental disorders caused by the loss or increase of MeCP2 function suggest that even modest alterations of MeCP2 protein levels result in neurodevelopmental problems. To determine whether a small reduction in MeCP2 level has phenotypic consequences, we characterized a conditional mouse allele of Mecp2 that expresses 50% of the wild-type level of MeCP2. Upon careful behavioral analysis, mice that harbor this allele display a spectrum of abnormalities such as learning and motor deficits, decreased anxiety, altered social behavior and nest building, decreased pain recognition and disrupted breathing patterns. These results indicate that precise control of MeCP2 is critical for normal behavior and predict that human neurodevelopmental disorders will result from a subtle reduction in MeCP2 expression. PMID:18321864

Gastrinomas associated with MEN-1 syndrome: new insights for the diagnosis and management in a series of 11 patients.

PubMed

Nikou, George C; Toubanakis, Christos; Nikolaou, Panagiota; Giannatou, Eleanna; Marinou, Kiriakoula; Safioleas, Michael; Karamanolis, Dimitrios

2005-01-01

Approximately, 25-30% of patients (pts) have gastrinomas, (Zollinger-Ellison syndrome, ZES), as part of the inherited syndrome, multiple endocrine neoplasia 1 (MEN-1). The identification of MEN-1 syndrome in these pts is always important, as there are some differences in their management and prognosis. Among 33 pts with ZES, we present in this study 11 pts with ZES and MEN-1 syndrome, describing our diagnostic and therapeutic approach. Eleven pts with ZES and MEN-1 syndrome (6 females and 5 males) were included (mean age 51.8 years). The diagnosis of ZES was based upon: a) clinical features and b) high serum gastrin levels, while in 7/11 pts diagnosis was confirmed histopathologically. A variety of other gastrointestinal peptides, as well as the general neuroendocrine tumor marker, Chromogranin-A (CgA) were also estimated. All pts underwent conventional imaging methods (CT, MRI) and OCTREOSCAN or EUS when necessary, in order to localize the primary lesion or the metastases. The diagnosis of MEN-1 was based upon the presence of the other two MEN-1 related endocrinopathies (hyperparathyroidism, pituitary adenomas), revealed by estimation of several hormones (PTH, Prolactin, ACTH etc.) and performance of imaging studies of the pituitary and parathyroid glands. When MEN-1 syndrome was established, a familiar screening of pts was also performed, when possible. The mean duration of pts' follow-up was 6.1 years (range: 2.1-8.5 years). At the time of presentation, 91% pts, had symptoms of peptic ulcer disease, refractory to treatment, while a history of colicky abdominal pain due to nephrolithiasis was also reported by 45% pts. Four of our pts had a blood relation. Serum gastrin levels at the time of diagnosis were greater than 1000pg/mL in 63.5% pts, while at the same time serum CgA levels were greater than 10 times the upper normal limit (<98ng/mL) in all pts. OCTREOSCAN and EUS revealed the primary tumor (in duodenum or pancreas) in 64% pts, in whom conventional methods showed no abnormalities at the same time. Parathyroid adenomas, pituitary adenomas and bronchial carcinoids were revealed in 11, 3 and 1 pts respectively, which were treated surgically. Also, surgical treatment of pancreatic or duodenal gastrinomas was performed in 54.5% pts, while pts who already had metastases (45%), or developed them during the follow-up period (18%), were treated by somatostatin analogues (63.6%) and chemotherapy (27.3%). Ten out of 11 pts are alive and in a good condition, whereas 1 patient died 2.8 years after diagnosis. Familiar screening revealed parathyroid adenomas in 4 children of our pts, which were treated surgically. MEN-1 syndrome should always be considered in pts with ZES. A precise preoperative localization of all pancreaticoduodenal lesions, in combination with a surgical exploration and management by experienced surgeons, seems to be curative in pts without distal metastases. Non-surgical treatment with somatostatin analogues and chemotherapy in pts with progressive disease seem to stabilize the disease, although further studies are needed. A close clinical and biochemical follow-up of all pts, as well as their family members, is necessary in order to reveal and treat all MEN-1 related endocrinopathies and especially PETs, in an early stage.

Functional sensibility assessment. Part II: Effects of sensory improvement on precise pinch force modulation after transverse carpal tunnel release.

PubMed

Hsu, Hsiu-Yun; Kuo, Li-Chieh; Chiu, Haw-Yen; Jou, I-Ming; Su, Fong-Chin

2009-11-01

Patients with median nerve compression at the carpal tunnel often have poor sensory afferents. Without adequate sensory modulation control, these patients frequently exhibit clumsy performance and excessive force output in the affected hand. We analyzed precision grip function after the sensory recovery of patients with carpal tunnel syndrome (CTS) who underwent carpal tunnel release (CTR). Thirteen CTS patients were evaluated using a custom-designed pinch device and conventional sensory tools before and after CTR to measure sensibility, maximum pinch strength, and anticipated pinch force adjustments to movement-induced load fluctuations in a pinch-holding-up activity. Based on these tests, five force-related parameters and sensory measurements were used to determine improvements in pinch performance after sensory recovery. The force ratio between the exerted pinch force and maximum load force of the lifting object was used to determine pinch force coordination and to prove that CTR enabled precision motor output. The magnitude of peak pinch force indicated an economic force output during manipulations following CTR. The peak pinch force, force ratio, and percentage of maximum pinch force also demonstrated a moderate correlation with the Semmes-Weinstein test. Analysis of these tests revealed that improved sensory function helped restore patients' performance in precise pinch force control evaluations. These results suggest that sensory information plays an important role in adjusting balanced force output in dexterous manipulation. (c) 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Botulinum toxin in trigeminal neuralgia.

PubMed

Castillo-Álvarez, Federico; Hernando de la Bárcena, Ignacio; Marzo-Sola, María Eugenia

2017-01-06

Trigeminal neuralgia is one of the most disabling facial pain syndromes, with a significant impact on patients' quality of life. Pharmacotherapy is the first choice for treatment but cases of drug resistance often require new strategies, among which various interventional treatments have been used. In recent years a new therapeutic strategy consisting of botulinum toxin has emerged, with promising results. We reviewed clinical cases and case series, open-label studies and randomized clinical trials examining the use of botulinum toxin for drug-refractory trigeminal neuralgia published in the literature. The administration of botulinum toxin has proven to be a safe and effective therapeutic strategy in patients with drug-refractory idiopathic trigeminal neuralgia, but many questions remain unanswered as to the precise role of botulinum toxin in the treatment of this disease. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Personalized Cardiovascular Medicine Today: A Food and Drug Administration/Center for Drug Evaluation and Research Perspective.

PubMed

Blaus, Alison; Madabushi, Rajanikanth; Pacanowski, Michael; Rose, Martin; Schuck, Robert N; Stockbridge, Norman; Temple, Robert; Unger, Ellis F

2015-10-13

Over the past decade, personalized medicine has received considerable attention from researchers, drug developers, and regulatory agencies. Personalized medicine includes identifying patients most likely to benefit and those most likely to experience adverse reactions in response to a drug, and tailoring therapy based on pharmacokinetics or pharmacodynamic response, as well. Perhaps most exciting is finding ways to identify likely responders through genetic, proteomic, or other tests, so that only likely responders will be treated. However, less precise methods such as identifying historical, demographic, or other indicators of increased or reduced responsiveness are also important aspects of personalized medicine. The cardiovascular field has not used many genetic or proteomic markers, but has regularly used prognostic variables to identify likely responders. The development of biomarker-based approaches to personalized medicine in cardiovascular disease has been challenging, in part, because most cardiovascular therapies treat acquired syndromes, such as acute coronary syndrome and heart failure, which develop over many decades and represent the end result of several pathophysiological mechanisms. More precise disease classification and greater understanding of individual variations in disease pathology could drive the development of targeted therapeutics. Success in designing clinical trials for personalized medicine will require the selection of patient populations with attributes that can be targeted or that predict outcome, and the use of appropriate enrichment strategies once such attributes are identified. Here, we describe examples of personalized medicine in cardiovascular disease, discuss its impact on clinical trial design, and provide insight into the future of personalized cardiovascular medicine from a regulatory perspective. © 2015 American Heart Association, Inc.

Non perianal fistulas in Crohn's disease and short bowel syndrome: what we can do?

PubMed

Zildzic, Muharem; Alibegovic, Ervin

2009-01-01

Crohn's disease (CD) is a lifelong disease arising from an interaction between genetic and environmental factors, but seen predominantly in the developed countries of the world. The precise etiology is unknown and therefore a causal treatment is not yet available. Fistulating Crohn's disease includes fistulas arising in the perianal area, together with those communicating between the intestine and other organs or the abdominal wall. Non perianal fistulas include fistulas communicating with other viscera (urinary bladder, vagina), loops of intestine (enteroenteral fistulas) or the abdominal wall (enterocutaneus fistulas). The diagnostic approach is a crucial aspect in the management of fistulating CD as the findings influence the therapeutic strategy. Short bowel syndrome caused by extensive bowel resection should be initially treated with nutritional support and can caused serious treatment and reevaluating problems. We review this uncommon manifestation in a high risk patient after multiple operations and severely shortened bowel and also with non perianal fistulating CD.

A common challenge in older adults: Classification, overlap, and therapy of depression and dementia.

PubMed

Leyhe, Thomas; Reynolds, Charles F; Melcher, Tobias; Linnemann, Christoph; Klöppel, Stefan; Blennow, Kaj; Zetterberg, Henrik; Dubois, Bruno; Lista, Simone; Hampel, Harald

2017-01-01

Late-life depression is frequently associated with cognitive impairment. Depressive symptoms are often associated with or even precede a dementia syndrome. Moreover, depressive disorders increase the risk of persistence for mild cognitive impairment and dementia. Here, we present both the current state of evidence and future perspectives regarding the integration and value of clinical assessments, neuropsychological, neurochemical, and neuroimaging biomarkers for the etiological classification of the dementia versus the depression syndrome and for the prognosis of depression relating to dementia risk. Finally, we summarize the existing evidence for both pharmacotherapy and psychotherapy of depression in demented patients. There is an urgent need for large-scale collaborative research to elucidate the role and interplay of clinical and biological features in elderly individuals with depressive disorders who are at elevated risk for developing dementia. To overcome barriers for successful drug development, we propose the introduction of the precision medicine paradigm to this research field. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Optimized methods for total nucleic acid extraction and quantification of the bat white-nose syndrome fungus, Pseudogymnoascus destructans, from swab and environmental samples.

PubMed

Verant, Michelle L; Bohuski, Elizabeth A; Lorch, Jeffery M; Blehert, David S

2016-03-01

The continued spread of white-nose syndrome and its impacts on hibernating bat populations across North America has prompted nationwide surveillance efforts and the need for high-throughput, noninvasive diagnostic tools. Quantitative real-time polymerase chain reaction (qPCR) analysis has been increasingly used for detection of the causative fungus, Pseudogymnoascus destructans, in both bat- and environment-associated samples and provides a tool for quantification of fungal DNA useful for research and monitoring purposes. However, precise quantification of nucleic acid from P. destructans is dependent on effective and standardized methods for extracting nucleic acid from various relevant sample types. We describe optimized methodologies for extracting fungal nucleic acids from sediment, guano, and swab-based samples using commercial kits together with a combination of chemical, enzymatic, and mechanical modifications. Additionally, we define modifications to a previously published intergenic spacer-based qPCR test for P. destructans to refine quantification capabilities of this assay. © 2016 The Author(s).

Secondary nerve lengthening to obtain full knee extension in popliteal pterygium syndrome.

PubMed

Boeckx, Willy; Misani, Marta; Vandermeeren, Liesbeth; Franck, Diane; Zirak, Christophe; Demey, Albert

2014-05-01

Microsurgical nerve lengthening was performed in two siblings presenting a popliteal pterigium syndrome with a knee flexion contracture of 80 degrees. After the first attempt for nerve lengthening and knee extension elsewhere, a repeated lengthening was required due to continuing tip-toe walking and recurrent knee contracture at the age of 3 years. An extensive external and internal interfascicular microsurgical neurolysis resulted in a lengthening of the nerves. A full length of leg procedure had to be performed, inclusive of Achilles tendon lengthening to obtain a complete extension of the knee and a 90-degree ankle flexion. Maintaining the leg in a fully extended position was obtained with a dynamic splinting in the first month after the operation. When timing the operation we have to consider the importance of adequate precision of the microsurgical neurolysis, down to the identification of the Fontana bands, and the adequate postoperative splinting. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

SHOX Haploinsufficiency as a Cause of Syndromic and Nonsyndromic Short Stature

PubMed Central

Fukami, Maki; Seki, Atsuhito; Ogata, Tsutomu

2016-01-01

SHOX in the short arm pseudoautosomal region (PAR1) of sex chromosomes is one of the major growth genes in humans. SHOX haploinsufficiency results in idiopathic short stature and Léri-Weill dyschondrosteosis and is associated with the short stature of patients with Turner syndrome. The SHOX protein likely controls chondrocyte apoptosis by regulating multiple target genes including BNP,Fgfr3, Agc1, and Ctgf. SHOX haploinsufficiency frequently results from deletions and duplications in PAR1 involving SHOX exons and/or the cis-acting enhancers, while exonic point mutations account for a small percentage of cases. The clinical severity of SHOX haploinsufficiency reflects hormonal conditions rather than mutation types. Growth hormone treatment seems to be beneficial for cases with SHOX haploinsufficiency, although the long-term outcomes of this therapy require confirmation. Future challenges in SHOX research include elucidating its precise function in the developing limbs, identifying additional cis-acting enhancers, and determining optimal therapeutic strategies for patients. PMID:27194967

Myocardial ischaemia and cardiac pain – a mysterious relationship

PubMed Central

Fisher, Mike

2013-01-01

Pain related to cardiac disease has been recognised for centuries. However, the precise mechanisms of angina pectoris remain bafflingly obscure. Conventional cardiological angina management concentrates on methods to improve oxygen delivery to cardiac myocytes as our understanding of cardiac muscle cells’ response to hypoxia increases. In common with other chronic visceral pain syndromes, little is understood about how pain signals are generated and propagated by visceral nerves. Improved imaging and other physiological assessments have demonstrated important central nervous system (CNS) responses to myocardial ischaemia, including activation of CNS areas known to be ‘key players’ in chronic pain syndromes. Patients with stable angina usually have an excellent prognosis, especially if left ventricular function is preserved. Educating patients about their condition, teaching simple techniques known to help chronic pain patients and introducing targeted pain treatments specific to angina can be extremely helpful adjuncts to conventional cardiological treatments and will often bring about significant improvements in quality of life. PMID:26516494

Optimized methods for total nucleic acid extraction and quantification of the bat white-nose syndrome fungus, Pseudogymnoascus destructans, from swab and environmental samples

USGS Publications Warehouse

Verant, Michelle; Bohuski, Elizabeth A.; Lorch, Jeffrey M.; Blehert, David

2016-01-01

The continued spread of white-nose syndrome and its impacts on hibernating bat populations across North America has prompted nationwide surveillance efforts and the need for high-throughput, noninvasive diagnostic tools. Quantitative real-time polymerase chain reaction (qPCR) analysis has been increasingly used for detection of the causative fungus, Pseudogymnoascus destructans, in both bat- and environment-associated samples and provides a tool for quantification of fungal DNA useful for research and monitoring purposes. However, precise quantification of nucleic acid fromP. destructans is dependent on effective and standardized methods for extracting nucleic acid from various relevant sample types. We describe optimized methodologies for extracting fungal nucleic acids from sediment, guano, and swab-based samples using commercial kits together with a combination of chemical, enzymatic, and mechanical modifications. Additionally, we define modifications to a previously published intergenic spacer–based qPCR test for P. destructans to refine quantification capabilities of this assay.

Case studies of uncommon headaches.

PubMed

Evans, Randolph W

2006-05-01

The following interesting and uncommon headache disorders are presented through case studies: exploding head syndrome, hypnic headache, neck-tongue syndrome, "Alice in Wonderland" syndrome, nummular headache, red ear syndrome, burning mouth syndrome, spontaneous intracranial hypotension syndrome, and cardiac cephalalgia.

PI3K/Akt Signaling Pathway Activates the WNK-OSR1/SPAK-NCC Phosphorylation Cascade in Hyperinsulinemic db/db Mice

PubMed Central

Nishida, Hidenori; Sohara, Eisei; Nomura, Naohiro; Chiga, Motoko; Alessi, Dario R; Rai, Tatemitsu; Sasaki, Sei; Uchida, Shinichi

2013-01-01

Metabolic syndrome patients have insulin resistance, which causes hyperinsulinemia, which in turn causes aberrant increased renal sodium reabsorption. The precise mechanisms underlying this greater salt-sensitivity of hyperinsulinemic patients remain unclear. Abnormal activation of the recently-identified WNK kinase-OSR1/SPAK kinases-NCC transporter phosphorylation cascade results in the salt-sensitive hypertension of pseudohypoaldosteronism type II. Here, we report a study of renal WNK-OSR1/SPAK-NCC cascade activation in the db/db mouse model of hyperinsulinemic metabolic syndrome. Thiazide sensitivity was increased, suggesting greater activity of NCC in db/db mice. In fact, increased phosphorylation of OSR1/SPAK and NCC was observed. In both SpakT243A/+ and Osr1T185A/+ knock-in db/db mice, which carry mutations that disrupt the signal from WNK kinases, increased phosphorylation of NCC and elevated blood pressure were completely corrected, indicating that phosphorylation of SPAK and OSR1 by WNK kinases is required for the increased activation and phosphorylation of NCC in this model. Renal phosphorylated Akt was increased in db/db mice, suggesting that increased NCC phosphorylation is regulated by the PI3K/Akt signaling cascade in the kidney in response to hyperinsulinemia. A PI3K inhibitor (NVP-BEZ235) corrected the increased OSR1/SPAK-NCC phosphorylation. Another more specific PI3K inhibitor (GDC-0941) and an Akt inhibitor (MK-2206) also inhibited increased NCC phosphorylation. These results indicate that the PI3K/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in db/db mice. This mechanism may play a role in the pathogenesis of salt-sensitive hypertension in human hyperinsulinemic conditions such as the metabolic syndrome. PMID:22949526

The cardiac troponins: uses in routine clinical practice. Experiences from GUSTO and other clinical trials.

PubMed

Stubbs, P

1998-11-01

Recent advances in pharmacological and mechanical approaches to acute coronary syndromes have led to rapid changes in the management of patients admitted with acute coronary syndromes. These changes have been mirrored by the appearance of newer highly specific biochemical markers of myocardial damage particularly the cardiac troponins. When new biochemical markers become available it is the responsibility of the clinical chemist to evaluate them critically in terms of sensitivity, specificity, efficiency and analyzer precision, in the rigid setting of quality control that laboratories practise, and to compare them with other markers. When the data are shown to Clinical Cardiologists with supporting statements such as 'useful management tool' and 'can be used for early diagnosis of Myocardial Infarction', a different set of questions may need to be answered. The 'So what?' response is most frequent and is the most important hurdle that these newer biochemical markers have to overcome to convince physicians to change their current practice. This presentation will review the results of studies that have examined the potential clinical usefulness of the cardiac troponins with respect to diagnosis and risk stratification of patients admitted with suspected acute coronary syndromes. Any troponin variable that survives the 'so what' question has one further major hurdle to overcome. This is the requirement to inform physicians what different therapeutic strategies they should follow if the variable is present. Available clinical trial evidence about differing management options for patients according to their troponin status will be reviewed and outline management algorithms will be presented. Many questions remain unanswered and these will be included at the time points where they may be relevant.

Novel CDKL5 Mutations in Czech Patients with Phenotypes of Atypical Rett Syndrome and Early-Onset Epileptic Encephalopathy.

PubMed

Záhoráková, D; Langová, M; Brožová, K; Laštůvková, J; Kalina, Z; Rennerová, L; Martásek, P

2016-01-01

The X-linked CDKL5 gene, which encodes cyclin-dependent kinase-like 5 protein, has been implicated in early-onset encephalopathy and atypical Rett syndrome with early-onset seizures. The CDKL5 protein is a kinase required for neuronal development and morphogenesis, but its precise functions are still largely unexplored. Individuals with CDKL5 mutations present with severe global developmental delay, intractable epilepsy, and Rett-like features. A clear genotype-phenotype correlation has not been established due to an insufficient number of reported cases. The aim of this study was to analyse the CDKL5 gene in Czech patients with early-onset seizures and Rett-like features. We performed mutation screening in a cohort of 83 individuals using high-resolution melting analysis, DNA sequencing and multiplex ligation- dependent probe amplification. Molecular analyses revealed heterozygous pathogenic mutations in three girls with severe intellectual disability and intractable epilepsy starting at the age of two months. All three identified mutations, c.637G>A, c.902_977+29del105, and c.1757_1758delCT, are novel, thus significantly extending the growing spectrum of known pathogenic CDKL5 sequence variants. Our results support the importance of genetic testing of the CDKL5 gene in patients with early-onset epileptic encephalopathy and Rett-like features with early-onset seizures. This is the first study referring to molecular defects of CDKL5 in Czech cases.

[Three-dimensional finite element study on the change of glossopharyngeum in patient with obstructive sleep apnea hypopnea syndrome during titrated mandible advancement].

PubMed

Yang, Suixing; Feng, Jing; Zhang, Zuo; Qu, Aili; Gong, Miao; Tang, Jie; Fan, Junheng; Li, Songqing; Zhao, Yanling

2013-04-01

To construct a three-dimensional finite element model of the upper airway and adjacent structure of an obstructive sleep apnea hypopnea syndrome (OSAHS) patient for biomechanical analysis. And to study the influence of glossopharyngeum of an OSAHS patient with three-dimensional finite element model during titrated mandible advancement. DICOM format image information of an OSAHS patient's upper airway was obtained by thin-section CT scanning and digital image processing were utilized to construct a three-dimensional finite element model by Mimics 10.0, Imageware 10.0 and Ansys software. The changes and the law of glossopharyngeum were observed by biomechanics and morphology after loading with titrated mandible advancement. A three-dimensional finite element model of the adjacent upper airway structure of OSAHS was established successfully. After loading, the transverse diameter of epiglottis tip of glossopharyngeum increased significantly, although the sagittal diameter decreased correspondingly. The principal stress was mainly distributed in anterior wall of the upper airway. The location of principal stress concentration did not change significantly with the increasing of distance. The stress of glossopharyngeum increased during titrated mandible advancement. A more precise three-dimensional finite model of upper airway and adjacent structure of an OSAHS patient is established and improved efficiency by Mimics, Imageware and Ansys software. The glossopharyngeum of finite element model of OSAHS is analyzed by titrated mandible advancement and can effectively show the relationship between mandible advancement and the glossopharyngeum.

Psychiatric disorders in a cohort of individuals with Prader-Willi syndrome.

PubMed

Shriki-Tal, L; Avrahamy, H; Pollak, Y; Gross-Tsur, V; Genstil, L; Hirsch, H J; Benarroch, F

2017-07-01

Psychiatric manifestations in Prader-Willi Syndrome (PWS) are common and often are the most debilitating problem in these individuals. We present an epidemiological nation-wide survey of psychiatric diagnoses in the PWS population, based on full-range psychiatric interviews. We studied the distribution of psychiatric diagnoses (as opposed to a symptom-based approach) in the Israel national cohort of adolescents and adults with PWS. There was a total of 53 (32 males) ages 12 years and older. All individuals and their caretakers were interviewed using standardized psychiatric questionnaires. Demographic and clinical variables, Clinical Global Impression (CGI) score, IQ, severity of hyperphagia and quality of life (QOL) were also assessed and correlations with NPD (number of psychiatric diagnoses) calculated. An overwhelming majority (89%) of the study participants had at least one psychiatric diagnosis. The most common were disruptive behavior disorders (DBD) (68%), obsessive compulsive disorder (OCD) (45%) and skin picking (35%). Individuals with DBD were at increased risk for OCD and skin picking. Psychotic disorders were found in 11%. NPD had a significant negative influence on QOL. There was no correlation between NPD and BMI, IQ, hyperphagia severity, hormonal profile or genetic subtypes. Psychiatric diagnoses are very frequent in PWS and strongly influence QOL. Furthermore, characterizing the profile of psychiatric comorbidity in PWS is crucial for planning effective interventions. Precise behavioral phenotyping in PWS in combination with a well-defined genetic etiology may aid biological research linking biological correlates to behavior. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Privacy Protection Versus Cluster Detection in Spatial Epidemiology

PubMed Central

Olson, Karen L.; Grannis, Shaun J.; Mandl, Kenneth D.

2006-01-01

Objectives. Patient data that includes precise locations can reveal patients’ identities, whereas data aggregated into administrative regions may preserve privacy and confidentiality. We investigated the effect of varying degrees of address precision (exact latitude and longitude vs the center points of zip code or census tracts) on detection of spatial clusters of cases. Methods. We simulated disease outbreaks by adding supplementary spatially clustered emergency department visits to authentic hospital emergency department syndromic surveillance data. We identified clusters with a spatial scan statistic and evaluated detection rate and accuracy. Results. More clusters were identified, and clusters were more accurately detected, when exact locations were used. That is, these clusters contained at least half of the simulated points and involved few additional emergency department visits. These results were especially apparent when the synthetic clustered points crossed administrative boundaries and fell into multiple zip code or census tracts. Conclusions. The spatial cluster detection algorithm performed better when addresses were analyzed as exact locations than when they were analyzed as center points of zip code or census tracts, particularly when the clustered points crossed administrative boundaries. Use of precise addresses offers improved performance, but this practice must be weighed against privacy concerns in the establishment of public health data exchange policies. PMID:17018828

Cardiac Autonomic Regulation in Autism and Fragile X Syndrome: A Review

PubMed Central

Klusek, Jessica; Roberts, Jane E.; Losh, Molly

2014-01-01

Despite the significance of efforts to understand the biological basis of autism, progress in this area has been hindered, in part, by the considerable heterogeneity in the disorder. Fragile X syndrome (FXS), a monogenic condition associated with high risk for autism, may pave the way for the dissection of biological heterogeneity within idiopathic autism. This paper adopts a cross-syndrome biomarker approach to evaluate potentially overlapping profiles of cardiac arousal dysregulation (and broader autonomic dysfunction) in autism and FXS. Approaches such as this, aimed at delineating shared mechanisms across genetic syndromes, hold great potential for improving diagnostic precision, promoting earlier identification, and uncovering key systems that can be targeted in pharmaceutical/behavioral interventions. Biomarker approaches may be vital to deconstructing complex psychiatric disorders, and are currently promoted as such by major research initiatives such as the NIMH Research Domain Criteria (RDoC). Evidence reviewed here supports physiological dysregulation in a subset of individuals with autism, as evidenced by patterns of hyperarousal and dampened parasympathetic vagal tone, which overlap with the well-documented physiological profile of FXS. Moreover, there is growing support for a link between aberrant cardiac activity and core deficits associated with autism, such as communication and social impairment. The delineation of physiological mechanisms common to autism and FXS could lend insight into relationships between genetic etiology and behavioral endstates, highlighting FMR1 as a potential candidate gene. Research gaps and potential pitfalls are discussed to inform timely, well-controlled biomarker research that will ultimately promote better diagnosis and treatment of autism and associated conditions. PMID:25420222

Constitutive activation of B-Raf in the mouse germ line provides a model for human cardio-facio-cutaneous syndrome.

PubMed

Urosevic, Jelena; Sauzeau, Vincent; Soto-Montenegro, María L; Reig, Santiago; Desco, Manuel; Wright, Emma M Burkitt; Cañamero, Marta; Mulero, Francisca; Ortega, Sagrario; Bustelo, Xosé R; Barbacid, Mariano

2011-03-22

RASopathies are a class of developmental syndromes that result from congenital mutations in key elements of the RAS/RAF/MEK signaling pathway. A well-recognized RASopathy is the cardio-facio-cutaneous (CFC) syndrome characterized by a distinctive facial appearance, heart defects, and mental retardation. Clinically diagnosed CFC patients carry germ-line mutations in four different genes, B-RAF, MEK1, MEK2, and K-RAS. B-RAF is by far the most commonly mutated locus, displaying mutations that most often result in constitutive activation of the B-RAF kinase. Here, we describe a mouse model for CFC generated by germ-line expression of a B-RafLSLV600E allele. This targeted allele allows low levels of expression of B-RafV600E, a constitutively active B-Raf kinase first identified in human melanoma. B-Raf+/LSLV600E mice are viable and display several of the characteristic features observed in CFC patients, including reduced life span, small size, facial dysmorphism, cardiomegaly, and epileptic seizures. These mice also show up-regulation of specific catecholamines and cataracts, two features detected in a low percentage of CFC patients. In addition, B-Raf+/LSLV600E mice develop neuroendocrine tumors, a pathology not observed in CFC patients. These mice may provide a means of better understanding the pathophysiology of at least some of the clinical features present in CFC patients. Moreover, they may serve as a tool to evaluate the potential therapeutic efficacy of B-RAF inhibitors and establish the precise window at which they could be effective against this congenital syndrome.

Wolfram (DIDMOAD) syndrome: a multidisciplinary clinical study in nine Turkish patients and review of the literature.

PubMed

Simsek, E; Simsek, T; Tekgül, S; Hosal, S; Seyrantepe, V; Aktan, G

2003-01-01

To study Wolfram syndrome (WFS) with multidisciplinary consultations and compare the results with the literature. Nine patients fulfilled the ascertainment criteria of WFS (insulin-dependent diabetes mellitus and optic atrophy). All patients were evaluated by the departments of paediatrics, ophthalmology, audiology, urology and medical biology. The earliest manifestation of WFS was insulin-dependent diabetes mellitus (at a median age of 6.9 y), followed by optic atrophy (8.9 y), diabetes insipidus (10.2 y) and deafness (10.5 y). Short stature was found in five cases, delayed puberty in two cases and hypergonadotropic hypogonadism in one case. Audiography disclosed hearing loss at high frequency in all patients (100%), but only five patients had clinical subjective hearing problems. Intravenous pyelography revealed hydroureteronephrosis in eight patients. Urodynamics revealed a normal bladder in only one patient. Three patients had a low-capacity, low-compliance bladder, detrusor external sphincteric dyssynergia and emptying problem, while five had an atonic bladder. Ocular findings were optic atrophy, low visual acuity and colour vision defects. Visual field tests revealed concentric and/or peripheral diminution in five patients. Visual evoked potentials were abnormal (reduced amplitude to both flash and pattern stimulation) in seven patients. Cranial magnetic resonance imaging showed mild or moderate atrophy of the optic nerves, chiasm, cerebellum, basal ganglia and brainstem in six patients; there was a partially empty sella in one case. There was no evidence of mitochondrial tRNA(Leu) (UUR) A to G (nucleotide 3243) mutation. Wolfram syndrome should be evaluated in a multidisciplinary manner. Some specific and dynamic tests are necessary to make a more precise estimate of the prevalence and median age of the components of WFS. Short stature is a common feature in WFS. Hypogonadism may be hypogonadotropic or hypergonadotropic. Bladder dysfunction does not always present as a large atonic bladder in WFS. A low-capacity, high-pressure bladder with sphincteric dyssynergia is also common.

Diagnostic accuracy of functional, imaging and biochemical tests for patients presenting with chest pain to the emergency department: A systematic review and meta-analysis.

PubMed

Iannaccone, Mario; Gili, Sebastiano; De Filippo, Ovidio; D'Amico, Salvatore; Gagliardi, Marco; Bertaina, Maurizio; Mazzilli, Silvia; Rettegno, Sara; Bongiovanni, Federica; Gatti, Paolo; Ugo, Fabrizio; Boccuzzi, Giacomo G; Colangelo, Salvatore; Prato, Silvia; Moretti, Claudio; D'Amico, Maurizio; Noussan, Patrizia; Garbo, Roberto; Hildick-Smith, David; Gaita, Fiorenzo; D'Ascenzo, Fabrizio

2018-01-01

Non-invasive ischaemia tests and biomarkers are widely adopted to rule out acute coronary syndrome in the emergency department. Their diagnostic accuracy has yet to be precisely defined. Medline, Cochrane Library CENTRAL, EMBASE and Biomed Central were systematically screened (start date 1 September 2016, end date 1 December 2016). Prospective studies (observational or randomised controlled trial) comparing functional/imaging or biochemical tests for patients presenting with chest pain to the emergency department were included. Overall, 77 studies were included, for a total of 49,541 patients (mean age 59.9 years). Fast and six-hour highly sensitive troponin T protocols did not show significant differences in their ability to detect acute coronary syndromes, as they reported a sensitivity and specificity of 0.89 (95% confidence interval 0.79-0.94) and 0.84 (0.74-0.9) vs 0.89 (0.78-0.94) and 0.83 (0.70-0.92), respectively. The addition of copeptin to troponin increased sensitivity and reduced specificity, without improving diagnostic accuracy. The diagnostic value of non-invasive tests for patients without troponin increase was tested. Coronary computed tomography showed the highest level of diagnostic accuracy (sensitivity 0.93 (0.81-0.98) and specificity 0.90 (0.93-0.94)), along with myocardial perfusion scintigraphy (sensitivity 0.85 (0.77-0.91) and specificity 0.92 (0.83-0.96)). Stress echography was inferior to coronary computed tomography but non-inferior to myocardial perfusion scintigraphy, while exercise testing showed the lower level of diagnostic accuracy. Fast and six-hour highly sensitive troponin T protocols provide an overall similar level of diagnostic accuracy to detect acute coronary syndrome. Among the non-invasive ischaemia tests for patients without troponin increase, coronary computed tomography and myocardial perfusion scintigraphy showed the highest sensitivity and specificity.

The eXtroardinarY Babies Study: Natural History of Health and Neurodevelopment in Infants and Young Children With Sex Chromosome Trisomy

ClinicalTrials.gov

2018-01-10

Klinefelter Syndrome; Trisomy X; XYY Syndrome; XXXY and XXXXY Syndrome; Xxyy Syndrome; Xyyy Syndrome; Xxxx Syndrome; Xxxxx Syndrome; Xxxyy Syndrome; Xxyyy Syndrome; Xyyyy Syndrome; Male With Sex Chromosome Mosaicism

Correlation Analysis between Traditional Chinese Medicine Syndromes and Gastrointestinal Bleeding after Percutaneous Coronary Intervention

PubMed Central

Huang, Chaolian; Wang, Mingming; Kong, Xiaolin; Liu, Guannan

2018-01-01

Objective To explore the characters of traditional Chinese medicine (TCM) syndromes after percutaneous coronary intervention (PCI) and to provide syndrome study theoretical evidence for TCM differentiation treatment after PCI through retrospective study. Methods Patients with coronary heart disease (CHD) who underwent PCI in Cardiovascular Intervention Center of Wangjing Hospital during Dec. 2012 to Dec. 2014 and met the inclusion criteria were enrolled. Retrospective study was then conducted based on patients' clinical document and angiography data to explore the distribution pattern of TCM syndromes. Results 801 patients were recruited in the study. TCM syndromes in descending order of their incidence were Qi deficiency and blood stasis syndrome, heart blood stasis syndrome, Qi and Yin deficiency syndrome, phlegm and blood stasis syndrome, Qi stagnation and blood stasis syndrome, Yang asthenia syndrome, heart and kidney yin deficiency syndrome to cold congeal, and blood stasis syndrome in a more to less order. Qi deficiency and blood stasis syndrome was in the most (occurring in 298 patients, 37.20%); Qi and Yin deficiency syndrome occurred in 163 patients (20.35%); heart blood stasis syndrome was shown in 126 patients (15.73%); phlegm and blood stasis syndrome was shown in 95 patients (11.86%). Conclusion Qi deficiency and blood stasis syndrome was closely associated with post-PCI bleeding, implying that this syndrome might serve as a powerful predictor of GI bleeding as well as a potential supplement to the current predicting and scoring system of bleeding such as CRUSADE.

Methylenetetrahydrofolate reductase and glutathione S-tranferase gene polymorphisms in secondary mixed phenotype acute leukemia: a case report.

PubMed

Skoric, Dejan; Ivana, Joksic; Tanja, Radic; Jovana, Jakovljevic; Petar, Ivanovski; Tatjana, Simic

2014-04-01

Therapy-induced leukemia is a well-known clinical syndrome occurring as a late complication in patients treated with cytotoxic therapy. We herein present results of analysis of common gene polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and glutathione S-transferase (GST) genes in a 10-year-old boy who developed very rare type of cancer, mixed phenotype acute leukemia, 6 years after treatment of acute lymphoblastic leukemia. Impairment in function of GST and MTHFR enzymes found in our patient may have contributed to the development of secondary mixed phenotype acute leukemia, although precise mechanism remains elusive.

The c.429_452 duplication of the ARX gene: a unique developmental-model of limb kinetic apraxia.

PubMed

Curie, Aurore; Nazir, Tatjana; Brun, Amandine; Paulignan, Yves; Reboul, Anne; Delange, Karine; Cheylus, Anne; Bertrand, Sophie; Rochefort, Fanny; Bussy, Gérald; Marignier, Stéphanie; Lacombe, Didier; Chiron, Catherine; Cossée, Mireille; Leheup, Bruno; Philippe, Christophe; Laugel, Vincent; De Saint Martin, Anne; Sacco, Silvia; Poirier, Karine; Bienvenu, Thierry; Souville, Isabelle; Gilbert-Dussardier, Brigitte; Bieth, Eric; Kauffmann, Didier; Briot, Philippe; de Fréminville, Bénédicte; Prieur, Fabienne; Till, Michel; Rooryck-Thambo, Caroline; Mortemousque, Isabelle; Bobillier-Chaumont, Isabelle; Toutain, Annick; Touraine, Renaud; Sanlaville, Damien; Chelly, Jamel; Freeman, Sonya; Kong, Jian; Hadjikhani, Nouchine; Gollub, Randy L; Roy, Alice; des Portes, Vincent

2014-02-14

The c.429_452dup24 of the ARX gene is a rare genetic anomaly, leading to X-Linked Intellectual Disability without brain malformation. While in certain cases c.429_452dup24 has been associated with specific clinical patterns such as Partington syndrome, the consequence of this mutation has been also often classified as "non-specific Intellectual Disability". The present work aims at a more precise description of the clinical features linked to the c.429_452dup24 mutation. We clinically reviewed all affected patients identified in France over a five-year period, i.e. 27 patients from 12 different families. Detailed cognitive, behavioural, and motor evaluation, as well as standardized videotaped assessments of oro-lingual and gestural praxis, were performed. In a sub-group of 13 ARX patients, kinematic and MRI studies were further accomplished to better characterize the motor impairment prevalent in the ARX patients group. To ensure that data were specific to the ARX gene mutation and did not result from low-cognitive functioning per se, a group of 27 age- and IQ-matched Down syndrome patients served as control. Neuropsychological and motor assessment indicated that the c.429_452dup24 mutation constitutes a recognizable clinical syndrome: ARX patients exhibiting Intellectual Disability, without primary motor impairment, but with a very specific upper limb distal motor apraxia associated with a pathognomonic hand-grip. Patients affected with the so-called Partington syndrome, which involves major hand dystonia and orolingual apraxia, exhibit the most severe symptoms of the disorder. The particular "reach and grip" impairment which was observed in all ARX patients, but not in Down syndrome patients, was further characterized by the kinematic data: (i) loss of preference for the index finger when gripping an object, (ii) major impairment of fourth finger deftness, and (iii) a lack of pronation movements. This lack of distal movement coordination exhibited by ARX patients is associated with the loss of independent digital dexterity and is similar to the distortion of individual finger movements and posture observed in Limb Kinetic Apraxia. These findings suggest that the ARX c.429_452dup24 mutation may be a developmental model for Limb Kinetic Apraxia.

Effect of fructose-reduced diet in patients with irritable bowel syndrome, and its correlation to a standard fructose breath test.

PubMed

Berg, Leif Kyrre; Fagerli, Erik; Martinussen, Marit; Myhre, Arnt-Otto; Florholmen, Jon; Goll, Rasmus

2013-08-01

To perform a validation of dairy registrations for use as diagnostic tool in IBS and fructose malabsorption (FM). To investigate the precision of the fructose breath test (FBT) as compared with symptom score reduction on fructose-reduced diet (FRD) in a cohort of patients with Rome II defined irritable bowel syndrome (IBS). IBS patients diagnosed according to the Rome II criteria and with no organic gastrointestinal disease were enrolled. The patients were randomized in an open study design with a 2 week run-in on IBS diet, followed by 4 weeks w/wo additional FRD. FBT was performed in all patients. Dairy registrations of stool frequency and consistency as well as abdominal pain/discomfort and bloating on a visual analog scale (VAS) were performed during the whole study. A total of 182 subjects performed the study according to protocol (88 FRD, 94 controls). The VAS symptom registration performed well in validation procedures, whereas stool data showed less impressive characteristics. FRD improved symptom scores (abdominal pain/discomfort and bloating) significantly whereas no changes were observed in the control group. The effect of FRD on the stool frequency was modest but no effect was observed on the stool consistency. The FBT did not discriminate between patients with and without effect of FRD, and even in the group with a negative FBT significant improvement of symptom scores was observed. VAS measures yield reliable symptom evaluation in dairy registrations of IBS. FRD improves symptom scores in IBS patients independent of results from the FBT.

Tomographic phase analysis to detect the site of accessory conduction pathway in Wolff-Parkinson-White syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakajima, K.; Bunko, H.; Tada, A.

1984-01-01

Phase analysis has been applied to Wolff-Parkinson-White syndrome (WPW) to detect the site of accessory conduction pathway (ACP); however, there was a limitation to estimate the precise location of ACP by planar phase analysis. In this study, the authors applied phase analysis to gated blood pool tomography. Twelve patients with WPW who underwent epicardial mapping and surgical division of ACP were studied by both of gated emission computed tomography (GECT) and routine gated blood pool study (GBPS). The GBPS was performed with Tc-99m red blood cells in multiple projections; modified left anterior oblique, right anterior oblique and/or left lateral views.more » In GECT, short axial, horizontal and vertical long axial blood pool images were reconstructed. Phase analysis was performed using fundamental frequency of the Fourier transform in both GECT and GBPS images, and abnormal initial contractions on both the planar and tomographic phase analysis were compared with the location of surgically confirmed ACPs. In planar phase analysis, abnormal initial phase was identified in 7 out of 12 (58%) patients, while in tomographic phase analysis, the localization of ACP was predicted in 11 out of 12 (92%) patients. Tomographic phase analysis is superior to planar phase images in 8 out of 12 patients to estimate the location of ACP. Phase analysis by GECT can avoid overlap of blood pool in cardiac chambers and has advantage to identify the propagation of phase three-dimensionally. Tomographic phase analysis is a good adjunctive method for patients with WPW to estimate the site of ACP.« less

Study of a patient population investigated for excessive daytime sleepiness (EDS).

PubMed

Laffont, F; Mallet, A; Mayer, G; Meunier, S; Minz, M; N'Doye, S; Quilfen-Buzare, M A

2002-12-01

This study included all patients referred to the out-patient department of our sleep disorders centre from 1993 to 1999 on account of excessive daytime sleepiness (EDS). As a first step, patients in whom a diagnosis was established following appropriate polysomnography were excluded: this included sleep apnea syndrome, increased upper airway resistance syndrome, narcolepsy, periodic movements during sleep or other parasomnia, and epilepsy. Patients regularly taking psychotropic substances or with psychiatric disorders were also excluded. Finally, 128 patients remained in whom no clear diagnosis had been established for EDS, 70 women and 58 men, their ages ranging from 16 to 77 years. They underwent a 48-h recording (night 1-MSLT-night 2-continuous day). The aim of the study was to establish, define and characterise different groups of undiagnosed EDS patients using clinical, electrophysiological and immunological data with the help of hierarchical cluster analysis. Eight groups were characterised: group 1: mild hypersomnia type 1 (n = 11); group 2: hypersomnia frequently associated with HLA type DR2-DQw1 (n = 11); group 3: mild hypersomnia type 2 (n = 28); group 4: morning recovery from disrupted sleep (n = 19); group 5: young "long sleepers with difficulty at waking up" (n = 17); group 6: idiopathic hypersomnia (n = 15); group 7: poor or short sleepers since childhood (n = 8); group 8: older poor sleepers with a late onset of symptoms (n = 19). Characteristic features of these different groups provided consistent and objective arguments leading to a more precise diagnosis for these patients, and helped the initiation of appropriate management and treatment.

Food patch testing for irritable bowel syndrome.

PubMed

Stierstorfer, Michael B; Sha, Christopher T; Sasson, Marvin

2013-03-01

The traditional classification of irritable bowel syndrome (IBS) as a functional disorder has been challenged in recent years by evidence of ongoing low-grade gastrointestinal tract inflammation. Inflammation may alter gastrointestinal motility and thus be central to the pathogenesis of IBS. Many foods and food additives are known to cause allergic contact dermatitis. We hypothesize that allergenic foods and food additives may elicit a similar allergic reaction in the gastrointestinal tract, giving rise to symptoms suggestive of IBS. We sought to determine whether skin patch testing to a panel of foods and food additives may identify food allergens that may be responsible for symptoms of IBS. We performed skin patch testing to common allergenic foods and food additives on individuals with a history of or symptoms suggestive of IBS. We used patch test-guided avoidance diets to determine whether avoidance alleviates IBS symptoms. Thirty of the 51 study participants showed at least 1 doubtful or positive patch test result. Fourteen of the participants reported symptomatic improvement, ranging from slight to great, upon avoidance of the foods/food additives to which they reacted. Double-blind study design, inclusion of only patients with active IBS, larger sample size, more balanced gender distribution, testing of more foods/food additives, and longer duration of and more precise quantification of response to dietary avoidance are suggested for future studies. Allergic contact enteritis to ingested foods, food additives, or both may contribute to IBS symptoms. Patch testing may be useful in identifying the causative foods. Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Dynamic balance of excitation and inhibition rapidly modulates spike probability and precision in feed-forward hippocampal circuits

PubMed Central

Wahlstrom-Helgren, Sarah

2016-01-01

Feed-forward inhibitory (FFI) circuits are important for many information-processing functions. FFI circuit operations critically depend on the balance and timing between the excitatory and inhibitory components, which undergo rapid dynamic changes during neural activity due to short-term plasticity (STP) of both components. How dynamic changes in excitation/inhibition (E/I) balance during spike trains influence FFI circuit operations remains poorly understood. In the current study we examined the role of STP in the FFI circuit functions in the mouse hippocampus. Using a coincidence detection paradigm with simultaneous activation of two Schaffer collateral inputs, we found that the spiking probability in the target CA1 neuron was increased while spike precision concomitantly decreased during high-frequency bursts compared with a single spike. Blocking inhibitory synaptic transmission revealed that dynamics of inhibition predominately modulates the spike precision but not the changes in spiking probability, whereas the latter is modulated by the dynamics of excitation. Further analyses combining whole cell recordings and simulations of the FFI circuit suggested that dynamics of the inhibitory circuit component may influence spiking behavior during bursts by broadening the width of excitatory postsynaptic responses and that the strength of this modulation depends on the basal E/I ratio. We verified these predictions using a mouse model of fragile X syndrome, which has an elevated E/I ratio, and found a strongly reduced modulation of postsynaptic response width during bursts. Our results suggest that changes in the dynamics of excitatory and inhibitory circuit components due to STP play important yet distinct roles in modulating the properties of FFI circuits. PMID:27605532

A systematic review of genetic variants associated with metabolic syndrome in patients with schizophrenia.

PubMed

Malan-Müller, Stefanie; Kilian, Sanja; van den Heuvel, Leigh L; Bardien, Soraya; Asmal, Laila; Warnich, Louise; Emsley, Robin A; Hemmings, Sîan M J; Seedat, Soraya

2016-01-01

Metabolic syndrome (MetS) is a cluster of factors that increases the risk of cardiovascular disease (CVD), one of the leading causes of mortality in patients with schizophrenia. Incidence rates of MetS are significantly higher in patients with schizophrenia compared to the general population. Several factors contribute to this high comorbidity. This systematic review focuses on genetic factors and interrogates data from association studies of genes implicated in the development of MetS in patients with schizophrenia. We aimed to identify variants that potentially contribute to the high comorbidity between these disorders. PubMed, Web of Science and Scopus databases were accessed and a systematic review of published studies was conducted. Several genes showed strong evidence for an association with MetS in patients with schizophrenia, including the fat mass and obesity associated gene (FTO), leptin and leptin receptor genes (LEP, LEPR), methylenetetrahydrofolate reductase (MTHFR) gene and the serotonin receptor 2C gene (HTR2C). Genetic association studies in complex disorders are convoluted by the multifactorial nature of these disorders, further complicating investigations of comorbidity. Recommendations for future studies include assessment of larger samples, inclusion of healthy controls, longitudinal rather than cross-sectional study designs, detailed capturing of data on confounding variables for both disorders and verification of significant findings in other populations. In future, big genomic datasets may allow for the calculation of polygenic risk scores in risk prediction of MetS in patients with schizophrenia. This could ultimately facilitate early, precise, and patient-specific pharmacological and non-pharmacological interventions to minimise CVD associated morbidity and mortality. Copyright © 2015 Elsevier B.V. All rights reserved.

Defining Precision Medicine Approaches to Autism Spectrum Disorders: Concepts and Challenges.

PubMed

Loth, Eva; Murphy, Declan G; Spooren, Will

2016-01-01

The tremendous clinical and etiological variability between individuals with autism spectrum disorder (ASD) has made precision medicine the most promising treatment approach. It aims to combine new pathophysiologically based treatments with objective tests (stratification biomarkers) to predict which treatment may be beneficial for a particular person. Here we discuss significant advances and current challenges for this approach: rare monogenic forms of ASD have provided a major breakthrough for the identification of treatment targets by providing a means to trace causal links from a gene to specific molecular alterations and biological pathways. To estimate whether treatment targets thus identified may be useful for larger patient groups we need a better understanding of whether different etiologies (i.e., genetic and environmental risk factors acting at different critical time points) lead to convergent or divergent molecular mechanisms, and how they map onto differences in circuit-level brain and cognitive development, and behavioral symptom profiles. Several recently failed clinical trials with syndromic forms of ASD provide valuable insights into conceptual and methodological issues linked to limitations in the translatability from animal models to humans, placebo effects, and a need for mechanistically plausible, objective outcome measures. To identify stratification biomarkers that enrich participant selection in clinical trials, large-scale multi-modal longitudinal observational studies are underway. Addressing these different factors in the next generation of research studies requires a translatable developmental perspective and multidisciplinary, collaborative efforts, with a commitment to sharing protocols and data, to increase transparency and reproducibility.

Immunohistochemical diagnosis of Alport's syndrome in paraffin-embedded renal sections: antigen retrieval with autoclave heating.

PubMed

Naito, Ichiro; Ninomiya, Yoshifumi; Nomura, Shinsuke

2003-03-01

Alport's syndrome (AS) is a hereditary renal disease caused by mutations in the genes encoding collagen type IV. Immunohistochemical analysis of the alpha chains of collagen type IV has been found to be useful for the diagnosis of this disease. The monoclonal antibodies (mAbs) generated by us recognize alpha 1(IV) through alpha 6(IV) chains of collagen type IV on fresh-frozen sections but not on paraffin-embedded sections. Antigen retrieval by autoclave heating has been found to restore the epitopes recognized by the mAbs; however the heating conditions had not been well established. In this study, the heating conditions were carefully examined using renal sections obtained from AS and non-AS patients. The heating was performed in an autoclave, at 105 degrees -127 degrees C for 6-8 min. During the heating, the sections were immersed in 0.2 N HCl solution (pH 0.9). Then, the mAbs were applied for 30 min, and the bound mAbs were detected using the LSAB kit. The optimal temperature for the antigen retrieval varied among specimens, and was dependent on the type of basement membrane examined. Thus, it was considered that heating at two or three different temperatures could be helpful for the precise diagnosis of AS. Adopting the antigen retrieval method could extend the possibility of immunohistochemical diagnosis of AS to cases without using fresh-frozen sections.

Gross and fine motor function in fibromyalgia and chronic fatigue syndrome.

PubMed

Rasouli, Omid; Fors, Egil A; Borchgrevink, Petter Chr; Öhberg, Fredrik; Stensdotter, Ann-Katrin

2017-01-01

This paper aimed to investigate motor proficiency in fine and gross motor function, with a focus on reaction time (RT) and movement skill, in patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS) compared to healthy controls (HC). A total of 60 individuals (20 CFS, 20 FM, and 20 HC), age 19-49 years, participated in this study. Gross motor function in the lower extremity was assessed using a RT task during gait initiation in response to an auditory trigger. Fine motor function in the upper extremity was measured during a precision task (the Purdue Pegboard test) where the number of pins inserted within 30 s was counted. No significant differences were found between FM and CFS in any parameters. FM and CFS groups had significantly longer RT than HC in the gait initiation ( p =0.001, and p =0.004 respectively). In the Purdue Pegboard test, 20% in the FM group, 15% in the CFS groups, and 0% of HC group, scored below the threshold of the accepted performance. However, there were no significant differences between FM, CFS, and HC in this task ( p =0.12). Compared to controls, both CFS and FM groups displayed significantly longer RT in the gait initiation task. Generally, FM patients showed the worst results in both tests, although no group differences were found in fine motor control, according to the Purdue Pegboard test.

Decidual Cox2 inhibition improves fetal and maternal outcomes in a preeclampsia-like mouse model

PubMed Central

Sones, Jenny L.; Cha, Jeeyeon; Woods, Ashley K.; Bartos, Amanda; Heyward, Christa Y.; Lob, Heinrich E.; Isroff, Catherine E.; Butler, Scott D.; Shapiro, Stephanie E.; Dey, Sudhansu K.; Davisson, Robin L.

2016-01-01

Preeclampsia (PE) is a disorder of pregnancy that manifests as late gestational maternal hypertension and proteinuria and can be life-threatening to both the mother and baby. It is believed that abnormal placentation is responsible for the cascade of events leading to the maternal syndrome. Embryo implantation is critical to establishing a healthy pregnancy. Defective implantation can cause adverse “ripple effects,” leading to abnormal decidualization and placentation, retarded fetal development, and poor pregnancy outcomes, such as PE and fetal growth restriction. The precise mechanism(s) of implantation defects that lead to PE remain elusive. BPH/5 mice, which spontaneously develop the cardinal features of PE, show peri-implantation defects including upregulation of Cox2 and IL-15 at the maternal-fetal interface. This was associated with decreased decidual natural killer (dNK) cells, which have important roles in establishing placental perfusion. Interestingly, a single administration of a Cox2 inhibitor (celecoxib) during decidualization restrained Cox2 and IL-15 expression, restored dNK cell numbers, improved fetal growth, and attenuated late gestational hypertension in BPH/5 female mice. This study provides evidence that decidual overexpression of Cox2 and IL-15 may trigger the adverse pregnancy outcomes reflected in the preeclamptic syndrome, underscoring the idea that Cox2 inhibitor treatment is an effective strategy for the prevention of PE-associated fetal and maternal morbidity and mortality. PMID:27159542

Hepatic encephalopathy

PubMed Central

2017-01-01

Abstract Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function occurring in patients with advanced liver diseases. The precise pathophysiology of HE is still under discussion; the leading hypothesis focus on the role of neurotoxins, impaired neurotransmission due to metabolic changes in liver failure, changes in brain energy metabolism, systemic inflammatory response and alterations of the blood brain barrier. HE produces a wide spectrum of nonspecific neurological and psychiatric manifestations. Minimal HE is diagnosed by abnormal psychometric tests. Clinically overt HE includes personality changes, alterations in consciousness progressive disorientation in time and space, somnolence, stupor and, finally, coma. Except for clinical studies, no specific tests are required for diagnosis. HE is classified according to the underlying disease, the severity of manifestations, its time course and the existence of precipitating factors. Treatment of overt HE includes supportive therapies, treatment of precipitating factors, lactulose and/or rifaximin. Routine treatment for minimal HE is only recommended for selected patients. PMID:28533911

Fifty Years of Research in ARDS. Genomic Contributions and Opportunities.

PubMed

Reilly, John P; Christie, Jason D; Meyer, Nuala J

2017-11-01

Clinical factors alone poorly explain acute respiratory distress syndrome (ARDS) risk and ARDS outcome. In the search for individual factors that may influence ARDS risk, the past 20 years have witnessed the identification of numerous genes and genetic variants that are associated with ARDS. The field of ARDS genomics has cycled from candidate gene association studies to bias-free approaches that identify new candidates, and increasing effort is made to understand the functional consequences that may underlie significant associations. More recently, methodologies of causal inference are being applied to maximize the information gained from genetic associations. Although challenges of sample size, both recognized and unrecognized phenotypic heterogeneity, and the paucity of early ARDS lung tissue limit some applications of the rapidly evolving field of genomic investigation, ongoing genetic research offers unique contributions to elucidating ARDS pathogenesis and the paradigm of precision ARDS medicine.

Psychiatric genetic research at the National Institute of Mental Health

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berg, K.; Mullican, C.; Maestri, N.

For some time it has been known through the results of family, twin, and adoption studies that hereditary appears to play a significant casual role in many mental disorders, including schizophrenia, bipolar disorder, and other mood disorders, Alzheimer`s Disease, panic disorder, obsessive compulsive disorder, autism, dyslexia, and Tourette`s syndrome. The precise patterns of inheritance of these complex disorders have not been determined, nor have the relevant genes been localized or cloned. Because the genetics are complex and because there is also clearly an environmental contribution to behavior, we expect the analysis of the genetics of mental illness to be arduousmore » and not quickly resolved. There are several compelling reasons to continue to focus our attention on uncovering the genetic factors for severe mental illness. Prominent among these are the implications for better treatment of mental disorders. The National Institute of Mental Health supports a wide range of studies on psychiatric genetic research. 16 refs.« less

Optical mapping of optogenetically shaped cardiac action potentials.

PubMed

Park, Sarah A; Lee, Shin-Rong; Tung, Leslie; Yue, David T

2014-08-19

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation.

Optical mapping of optogenetically shaped cardiac action potentials

PubMed Central

Park, Sarah A.; Lee, Shin-Rong; Tung, Leslie; Yue, David T.

2014-01-01

Light-mediated silencing and stimulation of cardiac excitability, an important complement to electrical stimulation, promises important discoveries and therapies. To date, cardiac optogenetics has been studied with patch-clamp, multielectrode arrays, video microscopy, and an all-optical system measuring calcium transients. The future lies in achieving simultaneous optical acquisition of excitability signals and optogenetic control, both with high spatio-temporal resolution. Here, we make progress by combining optical mapping of action potentials with concurrent activation of channelrhodopsin-2 (ChR2) or halorhodopsin (eNpHR3.0), via an all-optical system applied to monolayers of neonatal rat ventricular myocytes (NRVM). Additionally, we explore the capability of ChR2 and eNpHR3.0 to shape action-potential waveforms, potentially aiding the study of short/long QT syndromes that result from abnormal changes in action potential duration (APD). These results show the promise of an all-optical system to acquire action potentials with precise temporal optogenetics control, achieving a long-sought flexibility beyond the means of conventional electrical stimulation. PMID:25135113

SlgA, encoded by the homolog of the human schizophrenia-associated gene PRODH, acts in clock neurons to regulate Drosophila aggression

PubMed Central

Zwarts, Liesbeth; Vulsteke, Veerle; Buhl, Edgar; Hodge, James J. L.

2017-01-01

ABSTRACT Mutations in the proline dehydrogenase gene PRODH are linked to behavioral alterations in schizophrenia and as part of DiGeorge and velo-cardio-facial syndromes, but the role of PRODH in their etiology remains unclear. Here, we establish a Drosophila model to study the role of PRODH in behavioral disorders. We determine the distribution of the Drosophila PRODH homolog slgA in the brain and show that knockdown and overexpression of human PRODH and slgA in the lateral neurons ventral (LNv) lead to altered aggressive behavior. SlgA acts in an isoform-specific manner and is regulated by casein kinase II (CkII). Our data suggest that these effects are, at least partially, due to effects on mitochondrial function. We thus show that precise regulation of proline metabolism is essential to drive normal behavior and we identify Drosophila aggression as a model behavior relevant for the study of the mechanisms that are impaired in neuropsychiatric disorders. PMID:28331058

Sensory nerves are frequently involved in the spectrum of fisher syndrome.

PubMed

Shahrizaila, Nortina; Goh, Khean J; Kokubun, Norito; Tan, Ai H; Tan, Cheng Y; Yuki, Nobuhiro

2014-04-01

Differing patterns of neurophysiological abnormalities have been reported in patients with Fisher syndrome. Fisher syndrome is rare, and few series have incorporated prospective serial studies to define the natural history of nerve conduction studies in Guillain-Barré syndrome. In an ongoing prospective study of Guillain-Barré syndrome patients, patients who presented with Fisher syndrome and its spectrum of illness were assessed through serial neurological examinations, nerve conduction studies, and serological testing of IgG against gangliosides and ganglioside complexes. Of the 36 Guillain-Barré syndrome patients identified within 2 years, 17 had features of Fisher syndrome. Serial nerve conduction studies detected significant abnormalities in sensory nerve action potential amplitude in 94% of patients associated with 2 patterns of recovery-non-demyelinating reversible distal conduction failure and axonal regeneration. Similar changes were seen in motor nerves of 5 patients. Patients with the Fisher syndrome spectrum of illness have significant sensory involvement, which may only be evident with serial neurophysiological studies. Copyright © 2013 Wiley Periodicals, Inc.

Control of cellular influx in lung and its role in pulmonary toxicology.

PubMed Central

Lynn, W S

1984-01-01

The pulmonary influx of cytotoxic inflammatory cells, normally, in response to external toxins, is now thought to be etiologic in many of the disease syndromes of man, such as bronchitis and emphysema. Many types of effector inflammatory cells are involved, e.g., eosinophils, neutrophils, T-lymphocytes, monocytes. The diseases are characterized either by tissue destruction or by tissue hyperplasia. Agents which initiate the influx and cytotoxic secretions by these cells are legion and in general are not cell-specific. They include agents, such as phorbol esters, formyl peptides-complement fragments, elastin fragments, fatty acids (leukotrienes) as well as many uncharacterized excretions of inflammatory cells themselves, which react with specific receptors on the inflammatory cells, and secreted proteins such as fibronectin. Other agents, such as linoleic acid, digitonin and hydroxy fatty acids which are not bound by specific receptors also activate motility of inflammatory cells. The precise role of the above multiple cytotoxins in specific cellular fluxes in most pulmonary disease remains undefined. Similarly, the mechanism of cytotoxicity used by specific invading cells in specific pulmonary syndromes remains unclear. In general, macrophages are thought to destroy using specific proteases, neutrophils use oxidant radicals and proteases and eosinophils use basic surface active peptides. T-cells kill by unknown mechanisms. However, in specific clinical syndromes, it is usually not clear which cell is the cytotoxic culprit, nor is the mechanism of destruction usually known. PMID:6376103

Catatonia.

PubMed

Walther, Sebastian; Strik, Werner

2016-08-01

One of the most exciting psychiatric conditions is the bizarre psychomotor syndrome called catatonia, which may present with a large number of different motor signs and even vegetative instability. Catatonia is potentially life threatening. The use of benzodiazepines and electroconvulsive therapy (ECT) has been efficient in the majority of patients. The rich clinical literature of the past has attempted to capture the nature of catatonia. But the lack of diagnostic clarity and operationalization has hampered research on catatonia for a long time. Within the last decades, it became clear that catatonia had to be separated from schizophrenia, which was finally accomplished in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). In DSM-5, catatonia syndrome may be diagnosed as a specifier to major mood disorders, psychotic disorders, general medical conditions, and as catatonia not otherwise specified. This allows diagnosing the syndrome in a large variety of psychiatric disorders. Currently, the pathobiology remains widely unknown. Suspected neurotransmitter systems include gamma-aminobutyric acid (GABA) and glutamate. Neuroimaging reports pointed to reduced resting state activity and reduced task activation in motor areas of the frontal and parietal cortex. The new classification of catatonia will foster more clinical research and neuroscientific approaches by testing catatonia in various populations and applying stringent criteria. The scarce number of prospective trials will hopefully increase, as more trials will be encouraged within a more precise concept of catatonia.

Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers

PubMed Central

Baglietto, Laura; Dowty, James G.; White, Darren M.; Wagner, Anja; Gomez Garcia, Encarna B.; Vriends, Annette H. J. T.; Cartwright, Nicola R.; Barnetson, Rebecca A.; Farrington, Susan M.; Tenesa, Albert; Hampel, Heather; Buchanan, Daniel; Arnold, Sven; Young, Joanne; Walsh, Michael D.; Jass, Jeremy; Macrae, Finlay; Antill, Yoland; Winship, Ingrid M.; Giles, Graham G.; Goldblatt, Jack; Parry, Susan; Suthers, Graeme; Leggett, Barbara; Butz, Malinda; Aronson, Melyssa; Poynter, Jenny N.; Baron, John A.; Le Marchand, Loic; Haile, Robert; Gallinger, Steve; Hopper, John L.; Potter, John; de la Chapelle, Albert; Vasen, Hans F.; Dunlop, Malcolm G.; Thibodeau, Stephen N.; Jenkins, Mark A.

2010-01-01

Background Germline mutations in MSH6 account for 10%–20% of Lynch syndrome colorectal cancers caused by hereditary DNA mismatch repair gene mutations. Because there have been only a few studies of mutation carriers, their cancer risks are uncertain. Methods We identified 113 families of MSH6 mutation carriers from five countries that we ascertained through family cancer clinics and population-based cancer registries. Mutation status, sex, age, and histories of cancer, polypectomy, and hysterectomy were sought from 3104 of their relatives. Age-specific cumulative risks for carriers and hazard ratios (HRs) for cancer risks of carriers, compared with those of the general population of the same country, were estimated by use of a modified segregation analysis with appropriate conditioning depending on ascertainment. Results For MSH6 mutation carriers, the estimated cumulative risks to ages 70 and 80 years, respectively, were as follows: for colorectal cancer, 22% (95% confidence interval [CI] = 14% to 32%) and 44% (95% CI = 28% to 62%) for men and 10% (95% CI = 5% to 17%) and 20% (95% CI = 11% to 35%) for women; for endometrial cancer, 26% (95% CI = 18% to 36%) and 44% (95% CI = 30% to 58%); and for any cancer associated with Lynch syndrome, 24% (95% CI = 16% to 37%) and 47% (95% CI = 32% to 66%) for men and 40% (95% CI = 32% to 52%) and 65% (95% CI = 53% to 78%) for women. Compared with incidence for the general population, MSH6 mutation carriers had an eightfold increased incidence of colorectal cancer (HR = 7.6, 95% CI = 5.4 to 10.8), which was independent of sex and age. Women who were MSH6 mutation carriers had a 26-fold increased incidence of endometrial cancer (HR = 25.5, 95% CI = 16.8 to 38.7) and a sixfold increased incidence of other cancers associated with Lynch syndrome (HR = 6.0, 95% CI = 3.4 to 10.7). Conclusion We have obtained precise and accurate estimates of both absolute and relative cancer risks for MSH6 mutation carriers. PMID:20028993

Integration of Brain and Skull in Prenatal Mouse Models of Apert and Crouzon Syndromes

PubMed Central

Motch Perrine, Susan M.; Stecko, Tim; Neuberger, Thomas; Jabs, Ethylin W.; Ryan, Timothy M.; Richtsmeier, Joan T.

2017-01-01

The brain and skull represent a complex arrangement of integrated anatomical structures composed of various cell and tissue types that maintain structural and functional association throughout development. Morphological integration, a concept developed in vertebrate morphology and evolutionary biology, describes the coordinated variation of functionally and developmentally related traits of organisms. Syndromic craniosynostosis is characterized by distinctive changes in skull morphology and perceptible, though less well studied, changes in brain structure and morphology. Using mouse models for craniosynostosis conditions, our group has precisely defined how unique craniosynostosis causing mutations in fibroblast growth factor receptors affect brain and skull morphology and dysgenesis involving coordinated tissue-specific effects of these mutations. Here we examine integration of brain and skull in two mouse models for craniosynostosis: one carrying the FGFR2c C342Y mutation associated with Pfeiffer and Crouzon syndromes and a mouse model carrying the FGFR2 S252W mutation, one of two mutations responsible for two-thirds of Apert syndrome cases. Using linear distances estimated from three-dimensional coordinates of landmarks acquired from dual modality imaging of skull (high resolution micro-computed tomography and magnetic resonance microscopy) of mice at embryonic day 17.5, we confirm variation in brain and skull morphology in Fgfr2cC342Y/+ mice, Fgfr2+/S252W mice, and their unaffected littermates. Mutation-specific variation in neural and cranial tissue notwithstanding, patterns of integration of brain and skull differed only subtly between mice carrying either the FGFR2c C342Y or the FGFR2 S252W mutation and their unaffected littermates. However, statistically significant and substantial differences in morphological integration of brain and skull were revealed between the two mutant mouse models, each maintained on a different strain. Relative to the effects of disease-associated mutations, our results reveal a stronger influence of the background genome on patterns of brain-skull integration and suggest robust genetic, developmental, and evolutionary relationships between neural and skeletal tissues of the head. PMID:28790902

Management of genetic epilepsies: From empirical treatment to precision medicine.

PubMed

Striano, Pasquale; Vari, Maria Stella; Mazzocchetti, Chiara; Verrotti, Alberto; Zara, Federico

2016-05-01

Despite the over 20 antiepileptic drugs (AEDs) now licensed for epilepsy treatment, seizures can be effectively controlled in about ∼70% of patients. Thus, epilepsy treatment is still challenging in about one third of patients and this may lead to a severe medically, physically, and socially disabling condition. However, there is clear evidence of heterogeneity of response to existing AEDs and a significant unmet need for effective intervention. A number of studies have shown that polymorphisms may influence the poor or inadequate therapeutic response as well as the occurrence of adverse effects. In addition, the new frontier of genomic technologies, including chromosome microarrays and next-generation sequencing, improved our understanding of the genetic architecture of epilepsies. Recent findings in some genetic epilepsy syndromes provide insights into mechanisms of epileptogenesis, unrevealing the role of a number of genes with different functions, such as ion channels, proteins associated to the vesical synaptic cycle or involved in energy metabolism. The rapid progress of high-throughput genomic sequencing and corresponding analysis tools in molecular diagnosis are revolutionizing the practice and it is a fact that for some monogenic epilepsies the molecular confirmation may influence the choice of the treatment. Moreover, the novel genetic methods, that are able to analyze all known genes at a reasonable price, are of paramount importance to discover novel therapeutic avenues and individualized (or precision) medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

[On establishing comparative reference system for syndrome classification study from the thinking characteristics of syndrome differentiation dependent therapy].

PubMed

Liu, Ping; Hu, Yi-yang; Ni, Li-qiang

2006-05-01

To create a comparative referential system for syndrome classification study by viewing from the thinking characteristics of TCM on syndrome differentiation dependent therapy (SDDT), through analyzing the thinking process of SDDT, and the basic features of disease, syndrome and prescription, combining the basic principles of modern evidence-based medicine and feasibility of establishing integrative disease-syndrome animal model. The practice of creating a comparative referential system based on clinical efficacy of prescription was discussed around syndrome pathogenesis and its relationship with disease and prescription, which was one of the important scientific problems in TCM syndrome study. The authors hold that, it may be one of the available approaches for the present study on integration of disease with syndrome by way of insisting on the thinking pathway of stressing the characteristics of TCM and intermerging with modern scientific design; on taking the efficacy of prescription as the comparative reference system to accumulate and improve unceasingly according to the TCM method of syndrome diagnosis inferred from effect of prescription with reverse thought (i.e., to differentiate syndrome from the effect of prescription), and thus build up the syndrome diagnostic standard on the solid clinical and scientific base.

Mutations in CDC45, Encoding an Essential Component of the Pre-initiation Complex, Cause Meier-Gorlin Syndrome and Craniosynostosis.

PubMed

Fenwick, Aimee L; Kliszczak, Maciej; Cooper, Fay; Murray, Jennie; Sanchez-Pulido, Luis; Twigg, Stephen R F; Goriely, Anne; McGowan, Simon J; Miller, Kerry A; Taylor, Indira B; Logan, Clare; Bozdogan, Sevcan; Danda, Sumita; Dixon, Joanne; Elsayed, Solaf M; Elsobky, Ezzat; Gardham, Alice; Hoffer, Mariette J V; Koopmans, Marije; McDonald-McGinn, Donna M; Santen, Gijs W E; Savarirayan, Ravi; de Silva, Deepthi; Vanakker, Olivier; Wall, Steven A; Wilson, Louise C; Yuregir, Ozge Ozalp; Zackai, Elaine H; Ponting, Chris P; Jackson, Andrew P; Wilkie, Andrew O M; Niedzwiedz, Wojciech; Bicknell, Louise S

2016-07-07

DNA replication precisely duplicates the genome to ensure stable inheritance of genetic information. Impaired licensing of origins of replication during the G1 phase of the cell cycle has been implicated in Meier-Gorlin syndrome (MGS), a disorder defined by the triad of short stature, microtia, and a/hypoplastic patellae. Biallelic partial loss-of-function mutations in multiple components of the pre-replication complex (preRC; ORC1, ORC4, ORC6, CDT1, or CDC6) as well as de novo stabilizing mutations in the licensing inhibitor, GMNN, cause MGS. Here we report the identification of mutations in CDC45 in 15 affected individuals from 12 families with MGS and/or craniosynostosis. CDC45 encodes a component of both the pre-initiation (preIC) and CMG helicase complexes, required for initiation of DNA replication origin firing and ongoing DNA synthesis during S-phase itself, respectively, and hence is functionally distinct from previously identified MGS-associated genes. The phenotypes of affected individuals range from syndromic coronal craniosynostosis to severe growth restriction, fulfilling diagnostic criteria for Meier-Gorlin syndrome. All mutations identified were biallelic and included synonymous mutations altering splicing of physiological CDC45 transcripts, as well as amino acid substitutions expected to result in partial loss of function. Functionally, mutations reduce levels of full-length transcripts and protein in subject cells, consistent with partial loss of CDC45 function and a predicted limited rate of DNA replication and cell proliferation. Our findings therefore implicate the preIC as an additional protein complex involved in the etiology of MGS and connect the core cellular machinery of genome replication with growth, chondrogenesis, and cranial suture homeostasis. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management.

PubMed

Bierzynska, Agnieszka; McCarthy, Hugh J; Soderquest, Katrina; Sen, Ethan S; Colby, Elizabeth; Ding, Wen Y; Nabhan, Marwa M; Kerecuk, Larissa; Hegde, Shivram; Hughes, David; Marks, Stephen; Feather, Sally; Jones, Caroline; Webb, Nicholas J A; Ognjanovic, Milos; Christian, Martin; Gilbert, Rodney D; Sinha, Manish D; Lord, Graham M; Simpson, Michael; Koziell, Ania B; Welsh, Gavin I; Saleem, Moin A

2017-04-01

Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis. Pediatric patients with SRNS were identified via a national United Kingdom Renal Registry. Whole exome sequencing was performed on 187 patients, of which 12% have a positive family history with a focus on the 53 genes currently known to be associated with nephrotic syndrome. Genetic findings were correlated with individual case disease characteristics. Disease causing variants were detected in 26.2% of patients. Most often this occurred in the three most common SRNS-associated genes: NPHS1, NPHS2, and WT1 but also in 14 other genes. The genotype did not always correlate with expected phenotype since mutations in OCRL, COL4A3, and DGKE associated with specific syndromes were detected in patients with isolated renal disease. Analysis by primary/presumed compared with secondary steroid resistance found 30.8% monogenic disease in primary compared with none in secondary SRNS permitting further mechanistic stratification. Genetic SRNS progressed faster to end stage renal failure, with no documented disease recurrence post-transplantation within this cohort. Primary steroid resistance in which no gene mutation was identified had a 47.8% risk of recurrence. In this unbiased pediatric population, whole exome sequencing allowed screening of all current candidate genes. Thus, deep phenotyping combined with whole exome sequencing is an effective tool for early identification of SRNS etiology, yielding an evidence-based algorithm for clinical management. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Study on correspondence between prescription and syndrome and the essence of phlegm and blood stasis syndrome in coronary heart disease based on metabonomics.

PubMed

Lu, Xiao-yan; Xu, Hao; Li, Geng; Zhao, Tie

2014-01-01

Studying the essence of a syndrome has been a key challenge in the field of Chinese medicine. Until now, due to limitations of the methods available, the progress towards understanding such complicated systems has been slow. Metabonomics encompasses the dynamics, composition and analysis of metabolites, enabling the observation of changes in the metabolic network of the human body associated with disease. Being from the point of view of the whole organism, metabonomics provides an opportunity to study the essence of a syndrome to an unprecedented level. Phlegm and blood stasis syndrome is the main syndrome associated with coronary heart disease (CHD), which bring difficulties in clinical treatment due to difficulties associated with differentiation of symptoms and signs. The fundamental differences of material between the two also need to be interpreted. The authors consider that we can use the method of combining a disease (in this case CHD) with associated syndromes (phlegm and blood stasis syndrome) to select patients with phlegm and blood stasis syndrome of CHD, and utilize metabonomics to explore the essence of the syndrome by difference analysis of metabolite spectra. Meanwhile, we can study the syndrome in CM, observe the change regularity of metabolism spectra after the treatment of corresponding and non-corresponding prescription and syndrome, in order to validate the material fundament in the progress of syndrome formation and their differences. This will not only have great significance in enhancing the ability to identify syndrome of phlegm and blood stasis in CHD and to establish the clinical curative criteria, but will also offer a new approach of studying the essence for a syndrome using metabonomics.

Borderline personality disorder and polycystic ovary syndrome: A review of the literature.

PubMed

Tan, Raelene Ym; Grigg, Jasmin; Kulkarni, Jayashri

2018-02-01

This review examines the existing evidence for the relationship between borderline personality disorder and polycystic ovary syndrome, and to identify commonalities in etiological mechanisms of borderline personality disorder and polycystic ovary syndrome that might explain the relationship between these seemingly disparate disorders. A search of Medline, EMBASE and Cochrane Central was undertaken on 5 December 2016 to identify studies investigating women with borderline personality disorder and polycystic ovary syndrome (or symptoms and markers specific to polycystic ovary syndrome). Nine studies were identified, including three cross-sectional studies investigating symptoms of polycystic ovary syndrome in women with borderline personality disorder, two cross-sectional and one cohort study examining the prevalence of psychiatric diagnoses in women with polycystic ovary syndrome and three case reports of comorbid borderline personality disorder and polycystic ovary syndrome. Overall, the literature shows women with borderline personality disorder to have higher than expected serum androgen levels and incidence of polycystic ovaries, which can be key features of polycystic ovary syndrome. However, this research is still in its infancy, which limits our understanding of this potential comorbid phenomenon. Given the emerging anecdotal and empirical evidence to date, a theoretical discussion of the potential psychoneuroendocrinological mechanism underlying the borderline personality disorder and polycystic ovary syndrome comorbidity is provided. Further rigorous studies using standardized diagnostic criteria for polycystic ovary syndrome are warranted. Specifically, the use of prospective controlled cohort studies may be able to determine the causality and temporality of observed comorbid borderline personality disorder and polycystic ovary syndrome.

To bee or not to bee, this is the question…: The inborn numerical competence of humans and honeybees.

PubMed

Gross, Hans J

2011-09-01

Human inborn numerical competence means our ability to recognize object numbers precisely under circumstances which do not allow sequential counting. This archaic process has been called "subitizing," from the Latin "subito" = suddenly, immediately, indicating that the objects in question are presented to test persons only for a fraction of a second in order to prevent counting. In contrast, however, sequential counting, an outstanding cultural achievement of mankind, means to count "1, 2, 3, 4, 5, 6, 7, 8…" without a limit. The following essay will explain how the limit of numerical competence, i.e., the recognition of object numbers without counting, has been determined for humans and how this has been achieved for the first time in case of an invertebrate, the honeybee. Finally, a hypothesis explaining the influence of our limited, inborn numerical competence on counting in our times, e.g., in the Russian language, will be presented. Subitizing versus counting by young Down syndrome infants and autistics and the Savant syndrome will be discussed.

To bee or not to bee, this is the question…

PubMed Central

2011-01-01

Human inborn numerical competence means our ability to recognize object numbers precisely under circumstances which do not allow sequential counting. This archaic process has been called “subitizing,” from the Latin “subito” = suddenly, immediately, indicating that the objects in question are presented to test persons only for a fraction of a second in order to prevent counting. In contrast, however, sequential counting, an outstanding cultural achievement of mankind, means to count “1, 2, 3, 4, 5, 6, 7, 8…” without a limit. The following essay will explain how the limit of numerical competence, i.e., the recognition of object numbers without counting, has been determined for humans and how this has been achieved for the first time in case of an invertebrate, the honeybee. Finally, a hypothesis explaining the influence of our limited, inborn numerical competence on counting in our times, e.g., in the Russian language, will be presented. Subitizing versus counting by young Down syndrome infants and autistics and the Savant syndrome will be discussed. PMID:22046473

Cachexia: common, deadly, with an urgent need for precise definition and new therapies.

PubMed

Lainscak, Mitja; Filippatos, Gerasimos S; Gheorghiade, Mihai; Fonarow, Gregg C; Anker, Stefan D

2008-06-02

Cachexia--sometimes also referred to as wasting disease, malnutrition, or hypercatabolism--has been described for centuries and has always raised ominous thoughts that "the end is near." The disease is encountered in many malignant and nonmalignant chronic, ultimately fatal, illnesses. Yet, although cachexia is a deadly syndrome, little is known about its pathophysiology, and the debate regarding its definition is ongoing. Thus, the data on epidemiology can be contested, but a few things are certain: Cachexia is associated with exceedingly high mortality once the syndrome has fully developed, irrespective of the definition we apply, and it is associated with weakness, weight loss, muscle wasting, and inflammation. It is not simply an ancillary event, and it may contribute to the death of the patient either through effects on neuroendocrine and immune defense mechanisms or through protein calorie malnutrition. The therapeutic standard of care for cachexia remains undefined to date, with a few exceptions. Among the recognized approaches, exogenous oral amino acid supplementation appears very promising. Further research efforts are needed and they are ongoing.

Linkage analysis of the Nail-patella syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campeau, E.; Watkins, D.; Rouleau, G.A.

1995-01-01

Nail-patella syndrome (NPS) is an autosomal dominant disorder characterized by dysplasia of nails and patella, decreased mobility of the elbow, iliac horns, and, in some cases, nephropathy. The disorder has been mapped to the long arm of chromosome 9, but the precise localization and identity of the NPS gene are unknown. Linkage analysis in three NPS families, using highly informative dinucleotide repeat polymorphisms on 9q33-q34, confirmed linkage of NPS to this chromosome. Recombinations were detected, by two-point linkage analysis, between NPS and the centromeric markers D9S60 and the gelsolin gene and the telomeric markers D9S64 and D9S66, in one ofmore » the families. Haplotype analysis suggested an additional recombination between NPS and the argininosuccinate synthetase (ASS) gene. These results localize the NPS gene to an interval on 9q34.1, distal to D9S60 an proximal to ASS, comprising a genetic distance of {approximately}9 cM. This represents a significant refinement in the localization of the NPS gene. 25 refs., 2 figs., 1 tab.« less

Viewing Social Scenes: A Visual Scan-Path Study Comparing Fragile X Syndrome and Williams Syndrome

ERIC Educational Resources Information Center

Williams, Tracey A.; Porter, Melanie A.; Langdon, Robyn

2013-01-01

Fragile X syndrome (FXS) and Williams syndrome (WS) are both genetic disorders which present with similar cognitive-behavioral problems, but distinct social phenotypes. Despite these social differences both syndromes display poor social relations which may result from abnormal social processing. This study aimed to manipulate the location of…

Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders

PubMed Central

Kalberg, Wendy O.; Elliott, Amy J.; Blankenship, Jason; Buckley, David; Marais, Anna-Susan; Manning, Melanie A.; Robinson, Luther K.; Adam, Margaret P.; Abdul-Rahman, Omar; Jewett, Tamison; Coles, Claire D.; Chambers, Christina; Jones, Kenneth L.; Adnams, Colleen M.; Shah, Prachi E.; Riley, Edward P.; Charness, Michael E.; Warren, Kenneth R.; May, Philip A.

2016-01-01

The adverse effects of prenatal alcohol exposure constitute a continuum of disabilities (fetal alcohol spectrum disorders [FASD]). In 1996, the Institute of Medicine established diagnostic categories delineating the spectrum but not specifying clinical criteria by which diagnoses could be assigned. In 2005, the authors published practical guidelines operationalizing the Institute of Medicine categories, allowing for standardization of FASD diagnoses in clinical settings. The purpose of the current report is to present updated diagnostic guidelines based on a thorough review of the literature and the authors’ combined expertise based on the evaluation of >10 000 children for potential FASD in clinical settings and in epidemiologic studies in conjunction with National Institute on Alcohol Abuse and Alcoholism–funded studies, the Collaborative Initiative on Fetal Alcohol Spectrum Disorders, and the Collaboration on FASD Prevalence. The guidelines were formulated through conference calls and meetings held at National Institute on Alcohol Abuse and Alcoholism offices in Rockville, MD. Specific areas addressed include the following: precise definition of documented prenatal alcohol exposure; neurobehavioral criteria for diagnosis of fetal alcohol syndrome, partial fetal alcohol syndrome, and alcohol-related neurodevelopmental disorder; revised diagnostic criteria for alcohol-related birth defects; an updated comprehensive research dysmorphology scoring system; and a new lip/philtrum guide for the white population, incorporating a 45-degree view. The guidelines reflect consensus among a large and experienced cadre of FASD investigators in the fields of dysmorphology, epidemiology, neurology, psychology, developmental/behavioral pediatrics, and educational diagnostics. Their improved clarity and specificity will guide clinicians in accurate diagnosis of infants and children prenatally exposed to alcohol. PMID:27464676

A novel double recognition enzyme-linked immunosorbent assay based on the nucleocapsid protein for early detection of European porcine reproductive and respiratory syndrome virus infection.

PubMed

Venteo, A; Rebollo, B; Sarraseca, J; Rodriguez, M J; Sanz, A

2012-04-01

Precise and rapid detection of porcine reproductive respiratory syndrome virus (PRRSV) infection in swine farms is critical. Improvement of control procedures, such as testing incoming gilt and surveillance of seronegative herds requires more rapid and sensitive methods. However, standard serological techniques detect mainly IgG antibodies. A double recognition enzyme-linked immunosorbent assay (DR-ELISA) was developed for detection of antibodies specific to European PRRSV. This new assay can recognize both IgM and IgG antibodies to PRSSV which might be useful for detecting in routine surveillance assays pigs that are in the very early stages of infection and missed by conventional assays detecting only IgG antibodies. DR-ELISA is based on the double recognition of antigen by antibody. In this study, the recombinant nucleocapsid protein (N) of PRRSV was used both as the coating and the enzyme-conjugated antigen. To evaluate the sensitivity of the assay at early stages of the infection, sera from 69 pigs infected with PRRSV were collected during successive days post infection (pi) and tested. While standard methods showed low sensitivity rates before day 14 pi, DR-ELISA detected 88.4% seropositive samples at day 7 showing greater sensitivity at early stages of the infection. Further studies were carried out to assess the efficiency of the new assay, and the results showed DR-ELISA to be a sensitive and accurate method for early diagnosis of EU-PRRSV infection. Copyright © 2012 Elsevier B.V. All rights reserved.

Intergenerational associations of chronic disease and polycystic ovary syndrome.

PubMed

Davies, Michael J; Marino, Jennifer L; Willson, Kristyn J; March, Wendy A; Moore, Vivienne M

2011-01-01

Polycystic ovary syndrome (PCOS) is a common female endocrine disorder of heterogeneous clinical presentation, high disease burden, and unknown aetiology. The disease and associated conditions cluster in families, suggesting that PCOS may be the reproductive consequence of underlying chronic disease susceptibility. To determine whether parents of young women with PCOS were more likely to have a history of diabetes or cardiovascular disease in later adult life. Structured interviews with 715 members of a cohort constructed by tracing female infants born at a single general hospital in Adelaide between 1973 and 1975. Participants were asked whether they had a pre-existing medical diagnosis of PCOS, and whether each parent had ever had high blood pressure, high cholesterol, diabetes, stroke, or heart disease. Maternal high blood pressure during pregnancy was taken from the medical record of the pregnancy with the study participant. Mothers of women with PCOS were more likely than mothers of other women to have any cardiovascular disease (RR 1.78, 95% CI 1.29, 2.47), and nearly twice as likely to have high blood pressure (RR 1.95, 95% CI 1.38, 2.76). Fathers of women with PCOS were more than twice as likely to have heart disease (RR 2.36, 95% CI 1.44, 3.88) and over four times as likely to have had a stroke (RR 4.37, 95% CI 1.97, 9.70). Occurrence of cardiovascular disease in both mother and father are associated with the risk of PCOS in daughters. Further detailed study is required to elucidate the precise pathways that may be causally related to the observations.

Clinical importance of caffeine dependence and abuse.

PubMed

Ogawa, Naoshi; Ueki, Hirofumi

2007-06-01

Caffeine is the most widely consumed psychoactive substance and is a legal stimulant that is readily available to children. Caffeine has occasionally been considered a drug of abuse and the potential for dependence on caffeine has been debated. Presently, due to a paucity of clinical evidence on caffeine dependence or abuse, no such diagnosis is included in the Diagnostic and Statistical Manual of Mental Disorder-fourth edition. The authors present two cases of abuse or dependence on the caffeine contained in 'eutrophic' (energy/nutritional) beverages or caffeine preparations, followed by a review of clinical studies demonstrating evidence that some people can manifest a clinical syndrome of caffeine dependence or abuse. The cases suggest that caffeine can produce a clinical dependence syndrome similar to those produced by other psychoactive substances and has a potential for abuse. In a recent study using a structured interview and the Diagnostic and Statistical Manual of Mental Disorder-fourth edition criteria for substance dependence and abuse, a subset of the general population was found to demonstrate caffeine dependence or caffeine abuse. Therefore, the authors propose that companies or businesses manufacturing or marketing caffeine or products containing caffeine must meet the following guidelines: (i) clearly indicate the caffeine content of products containing comparatively higher quantities of caffeine; (ii) warn that such products should be avoided by infants and children wherever possible, and inform adult consumers about the precise quantity of caffeine that is considered safe for consumption; and (iii) clearly state that consuming large quantities of caffeine and the long-term use of caffeine carry health risks.

Acute exacerbation of idiopathic pulmonary fibrosis: lessons learned from acute respiratory distress syndrome?

PubMed

Marchioni, Alessandro; Tonelli, Roberto; Ball, Lorenzo; Fantini, Riccardo; Castaniere, Ivana; Cerri, Stefania; Luppi, Fabrizio; Malerba, Mario; Pelosi, Paolo; Clini, Enrico

2018-03-23

Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease characterized by progressive loss of lung function and poor prognosis. The so-called acute exacerbation of IPF (AE-IPF) may lead to severe hypoxemia requiring mechanical ventilation in the intensive care unit (ICU). AE-IPF shares several pathophysiological features with acute respiratory distress syndrome (ARDS), a very severe condition commonly treated in this setting.A review of the literature has been conducted to underline similarities and differences in the management of patients with AE-IPF and ARDS.During AE-IPF, diffuse alveolar damage and massive loss of aeration occurs, similar to what is observed in patients with ARDS. Differently from ARDS, no studies have yet concluded on the optimal ventilatory strategy and management in AE-IPF patients admitted to the ICU. Notwithstanding, a protective ventilation strategy with low tidal volume and low driving pressure could be recommended similarly to ARDS. The beneficial effect of high levels of positive end-expiratory pressure and prone positioning has still to be elucidated in AE-IPF patients, as well as the precise role of other types of respiratory assistance (e.g., extracorporeal membrane oxygenation) or innovative therapies (e.g., polymyxin-B direct hemoperfusion). The use of systemic drugs such as steroids or immunosuppressive agents in AE-IPF is controversial and potentially associated with an increased risk of serious adverse reactions.Common pathophysiological abnormalities and similar clinical needs suggest translating to AE-IPF the lessons learned from the management of ARDS patients. Studies focused on specific therapeutic strategies during AE-IPF are warranted.

Aspirin in the Chemoprevention of Colorectal Neoplasia: An Overview

PubMed Central

Chan, Andrew T.; Arber, Nadir; Burn, John; Chia, John Whay-Kuang; Elwood, Peter; Hull, Mark A.; Logan, Richard F.; Rothwell, Peter M.; Schrör, Karsten; Baron, John A.

2011-01-01

Considerable evidence supports the effectiveness of aspirin for chemoprevention of colorectal cancer (CRC) in addition to its well-established benefits in the prevention of vascular disease. Epidemiologic studies have consistently observed an inverse association between aspirin use and risk of CRC. A recent pooled analysis of a long-term post-trial follow-up of nearly 14,000 patients from 4 randomized, cardiovascular disease prevention trials showed that daily aspirin treatment for about 5 years was associated with a 34% reduction in 20-year CRC mortality. A separate meta-analysis of nearly 3,000 patients with a history of colorectal adenoma or cancer in 4 randomized adenoma prevention trials demonstrated that aspirin reduced the occurrence of advanced adenomas by 28% and any adenoma by 17%. Aspirin has also been shown to be beneficial in a clinical trial of patients with Lynch syndrome, a hereditary CRC syndrome; in those treated with aspirin for at least 2 years, there was a ≥ 50% reduction in the risk of CRC commencing 5 years after randomization and after aspirin had been discontinued. A few observational studies have shown an increase in survival among patients with CRC who use aspirin. Taken together, these findings strengthen the case for consideration of long-term aspirin use in CRC prevention. Despite these compelling data, there is a lack of consensus about the balance of risks and benefits associated with long-term aspirin use, particularly in low-risk populations. The optimal dose to use for cancer prevention and the precise mechanism underlying aspirin’s anticancer effect require further investigation. PMID:22084361

Delusions and the Right Hemisphere: A Review of the Case for the Right Hemisphere as a Mediator of Reality-Based Belief.

PubMed

Gurin, Lindsey; Blum, Sonja

2017-01-01

Delusions are beliefs that remain fixed despite evidence that they are incorrect. Although the precise neural mechanism of delusional belief remains to be elucidated, there is a predominance of right-hemisphere lesions among patients with delusional syndromes accompanied by structural pathology, suggesting that right-hemisphere lesions, or networks with key nodes in the right hemisphere, may be playing a role. The authors discuss the potential theoretical basis and empiric support for a specific right-hemisphere role in delusion production, drawing on its roles in pragmatic communication; perceptual integration; attentional surveillance and anomaly/novelty detection; and belief updating.

Analytical Method Development and Validation for the Simultaneous Estimation of Abacavir and Lamivudine by Reversed-phase High-performance Liquid Chromatography in Bulk and Tablet Dosage Forms.

PubMed

Raees Ahmad, Sufiyan Ahmad; Patil, Lalit; Mohammed Usman, Mohammed Rageeb; Imran, Mohammad; Akhtar, Rashid

2018-01-01

A simple rapid, accurate, precise, and reproducible validated reverse phase high performance liquid chromatography (HPLC) method was developed for the determination of Abacavir (ABAC) and Lamivudine (LAMI) in bulk and tablet dosage forms. The quantification was carried out using Symmetry Premsil C18 (250 mm × 4.6 mm, 5 μm) column run in isocratic way using mobile phase comprising methanol: water (0.05% orthophosphoric acid with pH 3) 83:17 v/v and a detection wavelength of 245 nm and injection volume of 20 μl, with a flow rate of 1 ml/min. In the developed method, the retention times of ABAC and LAMI were found to be 3.5 min and 7.4 min, respectively. The method was validated in terms of linearity, precision, accuracy, limits of detection, limits of quantitation, and robustness in accordance with the International Conference on Harmonization guidelines. The assay of the proposed method was found to be 99% - 101%. The recovery studies were also carried out and mean % recovery was found to be 99% - 101%. The % relative standard deviation from reproducibility was found to be <2%. The proposed method was statistically evaluated and can be applied for routine quality control analysis of ABAC and LAMI in bulk and in tablet dosage form. Attempts were made to develop RP-HPLC method for simultaneous estimation of Abacavir and Lamivudine for the RP-HPLC method. The developed method was validated according to the ICH guidelines. The linearity, precision, range, robustness were within the limits as specified by the ICH guidelines. Hence the method was found to be simple, accurate, precise, economic and reproducible. So the proposed methods can be used for the routine quality control analysis of Abacavir and Lamivudine in bulk drug as well as in formulations. Abbreviations Used: HPLC: High-performance liquid chromatography, UV: Ultraviolet, ICH: International Conference on Harmonization, ABAC: Abacavir, LAMI: Lamivudine, HIV: Human immunodeficiency virus, AIDS: Acquired immunodeficiency syndrome, NRTI: Nucleoside reverse transcriptase inhibitors, ARV: Antiretroviral, RSD: Relative standard deviation, RT: Retention time, SD: Standard deviation.

Assessing Energy Requirements in Women With Polycystic Ovary Syndrome: A Comparison Against Doubly Labeled Water.

PubMed

Broskey, Nicholas T; Klempel, Monica C; Gilmore, L Anne; Sutton, Elizabeth F; Altazan, Abby D; Burton, Jeffrey H; Ravussin, Eric; Redman, Leanne M

2017-06-01

Weight loss is prescribed to offset the deleterious consequences of polycystic ovary syndrome (PCOS), but a successful intervention requires an accurate assessment of energy requirements. Describe energy requirements in women with PCOS and evaluate common prediction equations compared with doubly labeled water (DLW). Cross-sectional study. Academic research center. Twenty-eight weight-stable women with PCOS completed a 14-day DLW study along with measures of body composition and resting metabolic rate and assessment of physical activity by accelerometry. Total daily energy expenditure (TDEE) determined by DLW. TDEE was 2661 ± 373 kcal/d. TDEE estimated from four commonly used equations was within 4% to 6% of the TDEE measured by DLW. Hyperinsulinemia (fasting insulin and homeostatic model assessment of insulin resistance) was associated with TDEE estimates from all prediction equations (both r = 0.45; P = 0.02) but was not a significant covariate in a model that predicts TDEE. Similarly, hyperandrogenemia (total testosterone, free androgen index, and dehydroepiandrosterone sulfate) was not associated with TDEE. In weight-stable women with PCOS, the following equation derived from DLW can be used to determine energy requirements: TDEE (kcal/d) = 438 - [1.6 * Fat Mass (kg)] + [35.1 * Fat-Free Mass (kg)] + [16.2 * Age (y)]; R2 = 0.41; P = 0.005. Established equations using weight, height, and age performed well for predicting energy requirements in weight-stable women with PCOS, but more precise estimates require an accurate assessment of physical activity. Our equation derived from DLW data, which incorporates habitual physical activity, can also be used in women with PCOS; however, additional studies are needed for model validation. Copyright © 2017 Endocrine Society

Modulation of Active Gut Microbiota by Lactobacillus rhamnosus GG in a Diet Induced Obesity Murine Model.

PubMed

Ji, Yosep; Park, Soyoung; Park, Haryung; Hwang, Eunchong; Shin, Hyeunkil; Pot, Bruno; Holzapfel, Wilhelm H

2018-01-01

Gut microbiota play a key role in the development of metabolic disorders. Defining and correlating structural shifts in gut microbial assemblages with conditions related to metabolic syndrome have, however, been proven difficult. Results from 16S genomic DNA and 16S ribosomal RNA analyses of fecal samples may differ widely, leading to controversial information on the whole microbial community and metabolically active microbiota. Using a C57BL/6J murine model, we compared data from 16S genomic DNA and ribosomal RNA of the fecal microbiota. The study included three groups of experimental animals comprising two groups with high fat diet induced obesity (DIO) while a third group (control) received a low fat diet. One of the DIO groups was treated with the probiotic Lactobacillus rhamnosus GG (LGG). Compared to the data obtained by DNA analysis, a significantly higher abundance of OTUs was accounted for by RNA analysis. Moreover, rRNA based analysis showed a modulation of the active gut microbial population in the DIO group receiving LGG, thus reflecting a change in the induced obesity status of the host. As one of the most widely studied probiotics the functionality of LGG has been linked to the alleviation of metabolic syndrome, and, in some cases, to an impact on the microbiome. Yet, it appears that no study has reported thus far on modulation of the active microbiota by LGG treatment. It is postulated that the resulting impact on calorie consumption affects weight gain concomitantly with modulation of the functional structure of the gut microbial population. Using the 16S rRNA based approach therefore decisively increased the precision of gut microbiota metagenome analysis.

Breast-fed infants and their later cardiovascular health: a prospective study from birth to age 32 years.

PubMed

Pirilä, Satu; Taskinen, Mervi; Viljakainen, Heli; Mäkitie, Outi; Kajosaari, Merja; Saarinen-Pihkala, Ulla M; Turanlahti, Maila

2014-03-28

The aim of the present study was to evaluate the impact of infant breast-feeding on cardiovascular risk in young adults. This unique study group involved 158 subjects (eighty-two females) originally collected prospectively at birth in 1975 and followed up to the age of 32 years. Frequent visits during the first year guaranteed the knowledge of the precise duration of breast-feeding. All infants received at least some breast milk. Participants were assessed for both individual cardiovascular risk factors (blood pressure, plasma lipids, homeostatic model assessment of insulin resistance and waist circumference) and the general clinical risk of cardiovascular events by calculating the Framingham risk score (FRS) and the metabolic syndrome criteria score (NCEP-ATPIII; National Cholesterol Education Program's Adult Treatment Panel III). Data on lifestyle factors were carefully collected. Linear regression analyses revealed that the effect of the duration of breast-feeding was not relevant (0·02 decrease in the FRS per one additional breast-feeding month; 95 % CI - 0·19, 0·09). Similarly, the effect of breast-feeding was minor on all of the individual cardiovascular risk factors. We used sex, physical activity, dietary fat and vitamin C, smoking and alcohol consumption as covariates. Again, logistic regression analyses detected no significant impact of the duration of breast-feeding on the risk of the metabolic syndrome according to the NCEP-ATPIII (OR 0·95, 95 % CI 0·8, 1·1). The strongest independent predictor for later CVD risk was male sex. In conclusion, in this prospectively followed cohort of young adults born at term and at weight appropriate for gestational age, the duration of breast-feeding did not have an impact on the accumulation of cardiovascular risk factors.

Goal-directed arm movements in children with fetal alcohol syndrome: a kinematic approach.

PubMed

Domellöf, E; Fagard, J; Jacquet, A-Y; Rönnqvist, L

2011-02-01

Although many studies have documented deficits in general motor functioning in children with fetal alcohol syndrome (FAS), few have employed detailed measurements to explore the specific nature of such disabilities. This pilot study explores whether three-dimensional (3D) kinematic analysis may generate increased knowledge of the effect of intrauterine alcohol exposure on motor control processes by detecting atypical upper-limb movement pattern specificity in children with FAS relative to typically developing (TD) children. Left and right arm and head movements during a sequential unimanual goal-directed precision task in a sample of children with FAS and in TD children were registered by an optoelectronic tracking system (ProReflex, Qualisys Inc.). Children with FAS demonstrated evidently poorer task performance compared with TD children. Additionally, analyses of arm movement kinematics revealed atypical spatio-temporal organization in the children with FAS. In general, they exhibited longer arm movement trajectories at both the proximal and distal level, faster velocities at the proximal level but slower at the distal level, and more segmented distal movements. Children with FAS also showed atypically augmented and fast head movements during the task performance. Findings indicate neuromotor deficits and developmental delay in goal-directed arm movements because of prenatal alcohol exposure. It is suggested that 3D kinematic analysis is a valid technique for furthering the understanding of motor control processes in children with FAS/fetal alcohol spectrum disorders. A combination with relevant neuroimaging techniques in future studies would enable a more clear-cut interpretation of how atypical movement patterns relate to underlying brain abnormalities. © 2010 The Author(s). European Journal of Neurology © 2010 EFNS.

Inner ear lesion and the differential roles of hypoxia and hypercarbia in triggering active movements: Potential implication for the Sudden Infant Death Syndrome.

PubMed

Ramirez, Sanja; Allen, Travis; Villagracia, Lindsay; Chae, Yooree; Ramirez, Jan M; Rubens, Daniel D

2016-11-19

Infants that succumb to Sudden Infant Death Syndrome (SIDS) have been identified with inner ear dysfunction (IED) at birth and on autopsy. We previously investigated whether IED could play a mechanistic role in SIDS. We discovered that animals with IED displayed significant suppression of movement arousal to a hypoxic-hypercarbic gas mixture under light anesthesia. In the current study we investigated the role of each gas in triggering movements and the response to hypercarbia during natural sleep without anesthesia. Seventeen-day-old CD-1 mice received intra-tympanic gentamicin (IT-Gent) injections to precipitate IED. The movement response to hypercarbia, hypoxia and hypoxia-hypercarbia was compared to controls under light anesthesia. Hypercarbia did not stimulate vigorous movements in any animals under either sleep condition. Hypoxia triggered vigorous movements in controls (p<0.05) and a decreased response in IT-Gent animals under light anesthesia. This contrasted with combined hypoxia-hypercarbia, in which IT-Gent animals displaced significantly suppressed movements compared to controls (p<0.05). Our findings portray that a degree of intact inner ear function is necessary for instigating the movement response. Additionally, hypoxia is the trigger for the movement response while carbon dioxide (CO 2 ) suppresses it. The finding that carbon dioxide did not stimulate movement during natural sleep is an important finding. This contrasts with other studies that have identified hypercarbia as an arousal stimulus with EEG. Further studies are warranted to evaluate the precise role of the inner ear in the movement response and potential association with SIDS. The early detection of IED in SIDS predisposed cases could be invaluable. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Gilles de la Tourette Syndrome, Depression, Depressive Illness, and Correlates in a Child and Adolescent Population.

PubMed

Rizzo, Renata; Gulisano, Mariangela; Martino, Davide; Robertson, Mary May

2017-04-01

Gilles de la Tourette syndrome (GTS) and depression are both common disorders. It has been suggested that depression occurs in 13%-76% GTS patients. Despite this, there are few studies into the specific relationships and correlates between the two disorders. There is only some consensus as to the precise relationship between the two disorders. We undertook the study to investigate the relationship between depressive symptomatology and the core clinical features of GTS in a well-characterized clinical population of youth with this disorder. Our aim was to verify the association between depression and comorbid obsessive-compulsive disorder and explore further other potential associations highlighted in some, but not all, of the studies focused on this topic. Our results demonstrated that (1) the GTS patients were significantly older than the controls, (2) the GTS patients were significantly more depressed than controls, (3) depression was associated with tic severity, (4) the Diagnostic Confidence Index scores were higher in GTS patients without depression, (5) anxiety, attention-deficit/hyperactivity disorder (ADHD), conduct disorder (CD), and behavioral problems were significantly associated with depression, and (6) finally, patients with GTS and depression have a positive family history of depression. However, obsessionality (CY-BOCS) did not differentiate between depressed and not depressed GTS patients. Depression is common in patients with GTS and occurs significantly more in GTS than in controls. Depression is significantly associated with GTS factors such as tic severity, comorbidity with ADHD, and the presence of coexistent anxiety, CDs, and behavior problems. Depression is importantly significantly associated with a positive family history of depression. Intriguingly, depression in our sample was not related to obsessionality.

Musical ear syndrome in adult cochlear implant patients.

PubMed

Low, W-K; Tham, C A; D'Souza, V-D; Teng, S-W

2013-09-01

Except for a single case report, musical ear syndrome in cochlear implantees has not been studied. We aimed to study the prevalence and nature of musical ear syndrome among adult cochlear implant patients, as well as the effect on their emotional well-being. STUDY DESIGN, PATIENTS AND INTERVENTION: A cross-sectional survey of patients aged 18 years and above who had received cochlear implants for profound hearing loss between 1997 and 2010. Of the 82 patients studied, 18 (22 per cent) were found to have experienced musical ear syndrome. Seven and 11 patients had musical ear syndrome prior to and after cochlear implantation, respectively. The character of musical ear syndrome symptoms was described as instrumental music (n = 2), singing (6) or both (10). Fourteen patients reported an adverse emotional effect, with three expressing ‘intolerance’. In this study, 22 per cent of cochlear implantees experienced musical ear syndrome. These symptoms affected patients’ emotional state, but most coped well. Musical ear syndrome can occur prior to and after cochlear implantation.

Thyroid function in adult Nigerians with metabolic syndrome.

PubMed

Udenze, Ifeoma; Nnaji, Ilochi; Oshodi, Temitope

2014-01-01

Metabolic syndrome and thyroid dysfunction are two common disorders encountered in the metabolic clinic. Recently, there has been increased interest in the association between the two disorders because of the similarities between symptoms of hypothyroidism and components of the metabolic syndrome. While some reports suggest that metabolic syndrome is associated with subclinical hypothyroidism, this concept is largely under investigated in Nigerian adults with metabolic syndrome. The aim of this study is to determine the thyroid function status of adult Nigerians with metabolic syndrome and determine the association, if any, between metabolic syndrome and thyroid function. This was a cross sectional study of one hundred and fifty adults, members of staff of the College of Medicine of the University of Lagos. The participants were recruited using a cluster random sampling method. The Ethical Research & Review Committee of the institution approved the study protocol and signed informed consent was obtained from the participants. The statistics was analysed using the IBM SPSS Software of version 19.0. The Student's t test, Chi square test and multivariate regression analysis were employed for the analysis. Statistical significance was set at p < 0.05. Thirty nine (twenty-six percent) of the study participants had metabolic syndrome and one hundred and eleven (seventy-four percent) of the study participants did not have metabolic syndrome, served as controls. Those who had metabolic syndrome group were significantly older (p = 0.03), metabolic syndrome was significantly associated with the female gender (p = 0.0002), higher systolic blood pressure (p = 0.0034), diastolic blood pressure (p = 0.0009), waist circumference (p < 0.0001), body mass index (p < 0.0001), waist-hip ratio (p = 0.003), fasting serum glucose (p = 0.0457) and free thyroxine (fT4) levels (p = 0.0496). Those with metabolic syndrome had significantly lower HDL (P = 0.004) and free triiodothyronine (fT3) levels (p = 0.037). There was no statistically significant difference in the thyroid stimulating hormone (TSH) levels between individuals with and without metabolic syndrome. Thirty-three percent of the metabolic syndrome cases had sick euthyroid syndrome (p= < 0.0001). In multivariate regression, waist circumference was significantly and inversely associated with the sick euthyroid syndrome (p = 0.011). Metabolic syndrome is associated with the sick euthyroid syndrome in adult Nigerians. Abdominal obesity appears to be the link between metabolic syndrome and the sick euthyroid syndrome.

[Study on qi deficiency syndrome distribution and quality of life in patients with advanced non-small cell lung cancer].

PubMed

Yuan, Lin; Zhang, Pei-tong; Yang, Zong-yan

2011-07-01

To study the qi deficiency syndrome distribution and quality of life (QOL) of patients with advanced non-small cell lung cancer (NSCLC). A questionnaire survey was conducted in 120 patients with advanced NSCLC using the QOL scale "Functional Assessment of Cancer Therapy" (FACT-L) (Version 4.0). Meanwhile, syndrome typing was performed. On the basis of results of syndrome typing, patients of different syndrome types were grouped and compared, thus studying the distribution of advanced NSCLC patients of qi deficiency syndrome and qi deficiency syndrome correlated QOL features. Qi deficiency, blood stasis, yin deficiency, phlegm and dampness dominated in syndrome types of the 120 patients with advanced NSCLC. Of syndrome types accounting for larger ratios in 112 patients, pure qi deficiency syndrome accounted for 30.36% (34 cases), qi deficiency and blood stasis syndrome for 18. 75% (21 cases), both qi and yin deficiency syndrome for 10. 71% (12 cases). There was no correlation between the appearance of qi deficiency syndrome and patients' age, sex, pathological typing (adenocarcinoma/squamous carcinoma), or the disease duration. NSCLC patients in phase IV were mostly complicated with qi deficiency syndrome (P<0.05). Scores of physical states, emotional states, functional states, and total scores in the FACT-L scale were lower in those complicated with qi deficiency syndrome (89 cases) than in those without complicated qi deficiency syndrome (31 cases), showing statistical difference (P<0.01, P<0.05). The scores of the lung cancer specific module (additional concerns) in the FACT-L scale showed statistical difference, sequenced as qi deficiency and blood stasis syndrome > pure qi deficiency syndrome > both qi and yin deficiency syndrome (P<0.05). Qi deficiency syndrome is the main syndrome of advanced NSCLC. The QOL of advanced NSCLC patients complicated with qi deficiency syndrome was poorer than those without complicated qi deficiency syndrome. Besides, along with the aggravation of qi deficiency syndrome, the QOL decreased somewhat. It suggested that symptomatic treatment of qi deficiency syndrome could improve advanced NSCLC patients' QOL.

Association of sleep quality components and wake time with metabolic syndrome: The Qazvin Metabolic Diseases Study (QMDS), Iran.

PubMed

Zohal, Mohammadali; Ghorbani, Azam; Esmailzadehha, Neda; Ziaee, Amir; Mohammadi, Zahrasadat

2017-11-01

The aim of this study was to determine the association of sleep quality and sleep quantity with metabolic syndrome in Qazvin, Iran. this cross sectional study was conducted in 1079 residents of Qazvin selected by multistage cluster random sampling method in 2011. Metabolic syndrome was defined according to the criteria proposed by the national cholesterol education program third Adult treatment panel. Sleep was assessed using the Pittsburgh sleep quality index (PSQI). A logistic regression analysis was used to examine the association of sleep status and metabolic syndrome. Mean age was 40.08±10.33years. Of 1079, 578 (52.2%) were female, and 30.6% had metabolic syndrome. The total global PSQI score in the subjects with metabolic syndrome was significantly higher than subjects without metabolic syndrome (6.30±3.20 vs. 5.83±2.76, P=0.013). In logistic regression analysis, sleep disturbances was associated with 1.388 fold increased risk of metabolic syndrome after adjustment for age, gender, and body mass index. Sleep disturbances component was a predictor of metabolic syndrome in the present study. More longitudinal studies are necessary to understand the association of sleep quality and its components with metabolic syndrome. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Dysmobility syndrome: current perspectives.

PubMed

Hill, Keith D; Farrier, Kaela; Russell, Melissa; Burton, Elissa

2017-01-01

A new term, dysmobility syndrome, has recently been described as a new approach to identify older people at risk of poor health outcomes. The aim was to undertake a systematic review of the existing research literature on dysmobility syndrome. All articles reporting dysmobility syndrome were identified in a systematic review of Medline (Proquest), CINAHL, PubMed, PsycInfo, EMBASE, and Scopus databases. Key characteristics of identified studies were extracted and summarized. The systematic review identified five papers (three cross-sectional, one case control, and one longitudinal study). No intervention studies were identified. Prevalence of dysmobility syndrome varied between studies (22%-34% in three of the studies). Dysmobility syndrome was shown to be associated with reduced function, increased falls and fractures, and a longitudinal study showed its significant association with mortality. Early research on dysmobility syndrome indicates that it may be a useful classification approach to identify older people at risk of adverse health outcomes and to target for early interventions. Future research needs to standardize the optimal mix of measures and cut points, and investigate whether balance performance may be a more useful factor than history of falls for dysmobility syndrome.

Genetic predisposition increases the tic severity, rate of comorbidities, and psychosocial and educational difficulties in children with Tourette syndrome.

PubMed

Eysturoy, Absalon Niclas; Skov, Liselotte; Debes, Nanette Mol

2015-03-01

This study aimed to examine whether there are differences in tic severity, comorbidities, and psychosocial and educational consequences in children with Tourette syndrome and genetic predisposition to Tourette syndrome compared with children with Tourette syndrome without genetic predisposition to Tourette syndrome. A total of 314 children diagnosed with Tourette syndrome participated in this study. Validated diagnostic tools were used to assess tic severity, comorbidities, and cognitive performance. A structured interview was used to evaluate psychosocial and educational consequences related to Tourette syndrome. The children with Tourette syndrome and genetic predisposition present with statistically significant differences in terms of severity of tics, comorbidities, and a range of psychosocial and educational factors compared with the children with Tourette syndrome without genetic predisposition. Professionals need to be aware of genetic predisposition to Tourette syndrome, as children with Tourette syndrome and genetic predisposition have more severe symptoms than those children with Tourette syndrome who are without genetic predisposition. © The Author(s) 2014.

Mathematics Learning Disability in Girls with Turner Syndrome or Fragile X Syndrome

ERIC Educational Resources Information Center

Murphy, Melissa M.; Mazzocco, Michele M. M.; Gerner, Gwendolyn; Henry, Anne E.

2006-01-01

Two studies were carried out to examine the persistence (Study 1) and characteristics (Study 2) of mathematics learning disability (MLD) in girls with Turner syndrome or fragile X during the primary school years (ages 5-9 years). In Study 1, the rate of MLD for each syndrome group exceeded the rate observed in a grade-matched comparison group,…

Brief Report: Repetitive Behaviour Profiles in Williams Syndrome: Cross Syndrome Comparisons with Prader-Willi and Down Syndromes

ERIC Educational Resources Information Center

Royston, R.; Oliver, C.; Moss, J.; Adams, D.; Berg, K.; Burbidge, C.; Howlin, P.; Nelson, L.; Stinton, C.; Waite, J.

2018-01-01

This study describes the profile of repetitive behaviour in individuals with Williams syndrome, utilising cross-syndrome comparisons with people with Prader-Willi and Down syndromes. The Repetitive Behaviour Questionnaire was administered to caregivers of adults with Williams (n = 96), Prader-Willi (n = 103) and Down (n = 78) syndromes. There were…

Velo-Cardio-Facial Syndrome: 30 Years of Study

ERIC Educational Resources Information Center

Shprintzen, Robert J.

2008-01-01

Velo-cardio-facial syndrome is one of the names that has been attached to one of the most common multiple anomaly syndromes in humans. The labels DiGeorge sequence, 22q11 deletion syndrome, conotruncal anomalies face syndrome, CATCH 22, and Sedlackova syndrome have all been attached to the same disorder. Velo-cardio-facial syndrome has an…

A Comparative Study of Educational Provision for Children with Neurogenetic Syndromes: Parent and Teacher Survey

ERIC Educational Resources Information Center

Reilly, C.; Senior, J.; Murtagh, L.

2015-01-01

Background: A number of neurogenetic syndromes have a high association with special educational needs including fragile X syndrome (FXS), Prader-Willi syndrome (PWS), Williams syndrome (WS) and Velo-Cardio-Facial syndrome (VCFS). There is a paucity of research on educational provision for children affected by these syndromes. Method: Parents…

Is a unified definition of metabolic syndrome needed? Comparison of three definitions of metabolic syndrome in 60-year-old men and women.

PubMed

Carlsson, Axel C; Wändell, Per E; Halldin, Mats; de Faire, Ulf; Hellénius, Mai-Lis

2009-06-01

There are three commonly used definitions of the metabolic syndrome, making scientific studies hard to compare. The aim of this study was to investigate agreement in the prevalence of the metabolic syndrome defined by three different definitions and to analyze definition and gender differences. A population-based, cross-sectional study of a total of 4232 participants--2039 men and 2193 women, aged 60 years--was employed. Three different metabolic syndrome definitions were compared: European Group for the Study of Insulin Resistance (EGIR), International Diabetes Federation (IDF), and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III). Medical history, socioeconomic information, and lifestyle data were collected by a questionnaire. A medical examination including laboratory tests was performed. Significant factors for the metabolic syndrome were calculated by multivariate logistic regression. Forty five percent of men and 30% of women met the criteria for the metabolic syndrome by any definition, but only 17% of men and 9% of women met the criteria of all three definitions. The highest agreement was found between IDF and NCEP ATP III definition. Two significant associations were identified in both men and women by the three metabolic syndrome definitions; former smokers were highly associated with the metabolic syndrome (odds ratio [OR] congruent with 1.5), and regular physical activity (OR congruent with 0.6) was inversely associated with the metabolic syndrome. Depending on the definition used, different individuals were identified as having the metabolic syndrome, which affects the reliability of interpretations to be made from scientific studies of the metabolic syndrome. Unified criteria are warranted. Physicians facing a physically inactive former smoker may consider diagnosing metabolic syndrome.

Birth characteristics of women with Marfan syndrome, obstetric and neonatal outcomes of their pregnancies-A nationwide cohort and case-control study.

PubMed

Kernell, Kristina; Sydsjö, Gunilla; Bladh, Marie; Josefsson, Ann

2017-08-01

The aim was to investigate birth characteristics, obstetric and neonatal outcomes of the first childbirth in women with Marfan syndrome by use of Swedish national registers since pregnancy-related outcomes in women with Marfan syndrome have only been sparsely investigated. In this national population-based cohort study and matched case-control study of Swedish women born 1973-1993, women with Marfan syndrome (n=273) were compared to women without the condition (n=1 017 265). The study population was followed until 2013. A total of 364 553 mother-firstborn-offspring pairs were analyzed. Sixty-one women with Marfan syndrome became mothers. Women with Marfan syndrome were also compared to 543 healthy controls. Women with Marfan syndrome were more often born preterm (p<0.001), small-for-gestational age (p<0.001), and delivered by cesarean section (p=0.001). Women with Marfan syndrome had no increased risk of giving birth by cesarean section (p=0.079). No increased neonatal risks in their children were found. Women with Marfan syndrome were less likely to give birth than those without (p<0.001). There were no maternal deaths. Women with Marfan syndrome were more likely to be born preterm, SGA and by cesarean section. These increased risks of preterm birth and SGA babies were not found in connection with their own first childbirth. Pregnancies with known fetal Marfan syndrome have to be carefully monitored. The results are important for obstetricians giving preconception counseling and treating women with Marfan syndrome. Further studies are needed to evaluate risks during pregnancy and long-term effects of pregnancy on the cardiovascular status of women with Marfan syndrome. Copyright © 2017 Elsevier B.V. All rights reserved.

Fibromyalgia: A Critical and Comprehensive Review.

PubMed

Borchers, Andrea T; Gershwin, M Eric

2015-10-01

Fibromyalgia is a disorder that is part of a spectrum of syndromes that lack precise classification. It is often considered as part of the global overview of functional somatic syndromes that are otherwise medically unexplained or part of a somatization disorder. Patients with fibromyalgia share symptoms with other functional somatic problems, including issues of myalgias, arthralgias, fatigue and sleep disturbances. Indeed, there is often diagnostic and classification overlap for the case definitions of a variety of somatization disorders. Fibromyalgia, however, is a critically important syndrome for physicians and scientists to be aware of. Patients should be taken very seriously and provided optimal care. Although inflammatory, infectious, and autoimmune disorders have all been ascribed to be etiological events in the development of fibromyalgia, there is very little data to support such a thesis. Many of these disorders are associated with depression and anxiety and may even be part of what has been sometimes called affected spectrum disorders. There is no evidence that physical trauma, i.e., automobile accidents, is associated with the development or exacerbation of fibromyalgia. Treatment should be placed on education, patient support, physical therapy, nutrition, and exercise, including the use of drugs that are approved for the treatment of fibromyalgia. Treatment should not include opiates and patients should not become poly pharmacies in which the treatment itself can lead to significant morbidities. Patients with fibromyalgia are living and not dying of this disorder and positive outlooks and family support are key elements in the management of patients.

Math Learning Disability and Math LD Subtypes: Evidence from Studies of Turner Syndrome, Fragile X Syndrome, and Neurofibromatosis Type 1.

ERIC Educational Resources Information Center

Mazzocco, Michele M. M.

2001-01-01

This study examined whether indicators of math learning disability were observed in 35 5- and 6-year-olds with either neurofibromatosis, Turner Syndrome, or fragile X syndrome and compared to controls. Findings indicate that girls with fragile X or Turner syndrome but not neurofibromatosis are significantly more likely to have specific math…

Direct versus indirect molecular diagnosis of fragile X mental retardation in 40 German families at risk.

PubMed

Knobloch, O; Pelz, F; Wick, U; Nelson, D L; Zoll, B

1993-03-01

In order to test whether the direct molecular diagnostic approach for fragile X mental retardation (Martin-Bell syndrome, MBS) really makes diagnosis of this disease more precise, we evaluated the results of direct diagnosis in 40 German families at risk together with the results of an earlier study with closely linked flanking markers in the same families. Of 84 men analysed, 43 showed clinical signs. In 39 of these affected men the disease could be confirmed by direct diagnosis. Compared to cytogenetic data, one man was false negative and two were false positive. Two men, whose status could not be determined by means of RFLP data, proved to be normal transmitting males (NTMs). However, the possibility of being an NTM had to be rejected in one case on RFLP data. Fragile X syndrome could be confirmed in 10 of the 13 women with clinical signs. Compared to cytogenetic data there were three cases of false negative results and one of false positive. All 36 obligate carrier women were detected by the direct approach. In addition, 22 women were newly identified as normal transmitting females (NTFs), among them one woman who could not be identified by cytogenetic means or by analysis with closely linked markers. These findings are discussed in view of the relative reliability of the three diagnostic approaches to MBS. Special attention is drawn to the significance of false negative and false positive results in direct diagnosis.

Gross and fine motor function in fibromyalgia and chronic fatigue syndrome

PubMed Central

Rasouli, Omid; Fors, Egil A; Borchgrevink, Petter Chr; Öhberg, Fredrik; Stensdotter, Ann-Katrin

2017-01-01

Purpose This paper aimed to investigate motor proficiency in fine and gross motor function, with a focus on reaction time (RT) and movement skill, in patients with fibromyalgia (FM) and chronic fatigue syndrome (CFS) compared to healthy controls (HC). Methods A total of 60 individuals (20 CFS, 20 FM, and 20 HC), age 19–49 years, participated in this study. Gross motor function in the lower extremity was assessed using a RT task during gait initiation in response to an auditory trigger. Fine motor function in the upper extremity was measured during a precision task (the Purdue Pegboard test) where the number of pins inserted within 30 s was counted. Results No significant differences were found between FM and CFS in any parameters. FM and CFS groups had significantly longer RT than HC in the gait initiation (p=0.001, and p=0.004 respectively). In the Purdue Pegboard test, 20% in the FM group, 15% in the CFS groups, and 0% of HC group, scored below the threshold of the accepted performance. However, there were no significant differences between FM, CFS, and HC in this task (p=0.12). Conclusion Compared to controls, both CFS and FM groups displayed significantly longer RT in the gait initiation task. Generally, FM patients showed the worst results in both tests, although no group differences were found in fine motor control, according to the Purdue Pegboard test. PMID:28223840

Advances in the processing of policromat images as diagnostic method to determine white spot syndrome virus in white shrimp (Litopenaeus vannamei)

NASA Astrophysics Data System (ADS)

Chavez-Sanchez, Cristina M.; Alvarez-Borrego, Josue; Montoya-Rodriguez, L.; Garcia-Gasca, A.; Fajer Avila, Emma J.; Pacheco-Marges, R.

2004-10-01

White spot syndrome (WSSV) is a viral disease which affects many crustacean species including commercial shrimps. Adequate, precise and quick methods to diagnose on time the presence of the disease in order to apply different strategies to avoid the dispersion and to reduce mortalities is necessary. Histopathology is an important diagnostic method. However, histopathology has the problem that requires time to prepare the histological slides and time to arrive to some diagnosis because this depend on the nature of the tissues, the pathogen(s) to find, the number of organisms, number of slides to analyze and the skill of the technician. This paper try to demonstrate the sensibility of one digital system of processing and recognition of images using color correlation with phase filters, to identify inclusion bodies of WSSV. Infected tissues were processed to obtain histological slides and to verify that the inclusion bodies observed were of WSV, in situ hybridization were carried out. The sensibility results of the recognition of the inclusion bodies of WSSV with the color correlation program was 86.1%. The highest percentage of recognition was in nervous system and tegument glands with 100%. The values in the stomach epithelium and heart tissue was 78.45% of recognition. Tissues with the lowest recognition values were lymphoid organ and hematopoietic tissue. It is necessary further studies to increase the sensibility and to obtain the specificity.

The Mechanism of Synchronous Precise Regulation of Two Shrimp White Spot Syndrome Virus Targets by a Viral MicroRNA

PubMed Central

He, Yaodong; Ma, Tiantian; Zhang, Xiaobo

2017-01-01

MicroRNAs (miRNAs), important factors in animal innate immunity, suppress the expressions of their target genes by binding to target mRNA’s 3′ untranslated regions (3′UTRs). However, the mechanism of synchronous regulation of multiple targets by a single miRNA remains unclear. In this study, the interaction between a white spot syndrome virus (WSSV) miRNA (WSSV-miR-N32) and its two viral targets (wsv459 and wsv322) was characterized in WSSV-infected shrimp. The outcomes indicated that WSSV-encoded miRNA (WSSV-miR-N32) significantly inhibited virus infection by simultaneously targeting wsv459 and wsv322. The silencing of wsv459 or wsv322 by siRNA led to significant decrease of WSSV copies in shrimp, showing that the two viral genes were required for WSSV infection. WSSV-miR-N32 could mediate 5′–3′ exonucleolytic digestion of its target mRNAs, which stopped at the sites of target mRNA 3′UTRs close to the sequence complementary to the miRNA seed sequence. The complementary bases (to the target mRNA sequence) of a miRNA 9th–18th non-seed sequence were essential for the miRNA targeting. Therefore, our findings presented novel insights into the mechanism of miRNA-mediated suppression of target gene expressions, which would be helpful for understanding the roles of miRNAs in innate immunity of invertebrate. PMID:29230209

Targeted exome sequencing reveals novel USH2A mutations in Chinese patients with simplex Usher syndrome.

PubMed

Shu, Hai-Rong; Bi, Huai; Pan, Yang-Chun; Xu, Hang-Yu; Song, Jian-Xin; Hu, Jie

2015-09-16

Usher syndrome (USH) is an autosomal recessive disorder characterized by hearing impairment and vision dysfunction due to retinitis pigmentosa. Phenotypic and genetic heterogeneities of this disease make it impractical to obtain a genetic diagnosis by conventional Sanger sequencing. In this study, we applied a next-generation sequencing approach to detect genetic abnormalities in patients with USH. Two unrelated Chinese families were recruited, consisting of two USH afflicted patients and four unaffected relatives. We selected 199 genes related to inherited retinal diseases as targets for deep exome sequencing. Through systematic data analysis using an established bioinformatics pipeline, all variants that passed filter criteria were validated by Sanger sequencing and co-segregation analysis. A homozygous frameshift mutation (c.4382delA, p.T1462Lfs*2) was revealed in exon20 of gene USH2A in the F1 family. Two compound heterozygous mutations, IVS47 + 1G > A and c.13156A > T (p.I4386F), located in intron 48 and exon 63 respectively, of USH2A, were identified as causative mutations for the F2 family. Of note, the missense mutation c.13156A > T has not been reported so far. In conclusion, targeted exome sequencing precisely and rapidly identified the genetic defects in two Chinese USH families and this technique can be applied as a routine examination for these disorders with significant clinical and genetic heterogeneity.

Contribution of domestic animals to the identification of new genes involved in sex determination.

PubMed

Pailhoux, E; Vigier, B; Vaiman, D; Schibler, L; Vaiman, A; Cribiu, E; Nezer, C; Georges, M; Sundström, J; Pelliniemi, L J; Fellous, M; Cotinot, C

2001-12-01

Among farm animals, two species present an intersex condition at a relatively high frequency: pig and goat. Both are known to contain XX sex-reversed individuals which are genetically female but with a true hermaphrodite or male phenotype. It has been clearly demonstrated that the SRY gene is not involved in these phenotypes. Consequently, autosomal or X-linked mutations in the sex-determining pathway may explain these sex-reversed phenotypes. A mutation referred to as "polled" has been characterized in goats by the suppression of horn formation and abnormal sexual differentiation. The Polled Intersex Syndrome locus (PIS) was initially located in the distal region of goat chromosome 1. The homologous human region has been precisely identified as an HSA 3q23 DNA segment containing the Blepharophimosis Ptosis Epicanthus locus (BPES), a syndrome combining Premature Ovarian Failure (POF) and an excess of epidermis of the eyelids. In order to isolate genes involved in pig intersexuality, a similar genetic approach was attempted in pigs using genome scanning of resource families. Genetic analyses suggest that pig intersexuality is controlled multigenically. Parallel to this work, gonads of fetal intersex animals have been studied during development by light and electron microscopy. The development of testicular tissue and reduction of germ cell number by apoptosis, which simultaneously occurs as soon as 50 days post coïtum, also suggests that several separate genes could be involved in pig intersexuality. Copyright 2001 Wiley-Liss, Inc.

Immunological Mechanisms Underlying Chronic Pelvic Pain and Prostate Inflammation in Chronic Pelvic Pain Syndrome

PubMed Central

Breser, María L.; Salazar, Florencia C.; Rivero, Viginia E.; Motrich, Rubén D.

2017-01-01

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain. PMID:28824626

Hemizygosity at the NCF1 Gene in Patients with Williams-Beuren Syndrome Decreases Their Risk of Hypertension

PubMed Central

Del Campo, Miguel; Antonell, Anna; Magano, Luis F.; Muñoz, Francisco J.; Flores, Raquel; Bayés, Mònica; Pérez Jurado, Luis A.

2006-01-01

Williams-Beuren syndrome (WBS), caused by a heterozygous deletion at 7q11.23, represents a model for studying hypertension, the leading risk factor for mortality worldwide, in a genetically determined disorder. Haploinsufficiency at the elastin gene is known to lead to the vascular stenoses in WBS and is also thought to predispose to hypertension, present in ∼50% of patients. Detailed clinical and molecular characterization of 96 patients with WBS was performed to explore clinical-molecular correlations. Deletion breakpoints were precisely defined and were found to result in variability at two genes, NCF1 and GTF2IRD2. Hypertension was significantly less prevalent in patients with WBS who had the deletion that included NCF1 (P=.02), a gene coding for the p47phox subunit of the NADPH oxidase. Decreased p47phox protein levels, decreased superoxide anion production, and lower protein nitrotyrosination were all observed in cell lines from patients hemizygous at NCF1. Our results indicate that the loss of a functional copy of NCF1 protects a proportion of patients with WBS against hypertension, likely through a lifelong reduced angiotensin II–mediated oxidative stress. Therefore, antioxidant therapy that reduces NADPH oxidase activity might have a potential benefit in identifiable patients with WBS in whom serious complications related to hypertension have been reported, as well as in forms of essential hypertension mediated by a similar pathogenic mechanism. PMID:16532385

Psychological Well-Being in Parents of Children with Angelman, Cornelia de Lange and Cri du Chat Syndromes

ERIC Educational Resources Information Center

Griffith, G. M.; Hastings, R. P.; Oliver, C.; Howlin, P.; Moss, J.; Petty, J.; Tunnicliffe, P.

2011-01-01

Background: The current study focuses on mothers and fathers of children with three rare genetic syndromes that are relatively unexplored in terms of family experience: Angelman syndrome, Cornelia de Lange syndrome and Cri du Chat syndrome. Method: Parents of children with Angelman syndrome (n = 15), Cornelia de Lange syndrome (n = 16) and Cri du…

The developmental trajectory of disruptive behavior in Down syndrome, fragile X syndrome, Prader-Willi syndrome and Williams syndrome.

PubMed

Rice, Lauren J; Gray, Kylie M; Howlin, Patricia; Taffe, John; Tonge, Bruce J; Einfeld, Stewart L

2015-06-01

The aim of this study was to investigate the developmental trajectories of verbal aggression, physical aggression, and temper tantrums in four genetic syndrome groups. Participants were part of the Australian Child to Adult Development Study (ACAD), which collected information from a cohort of individuals with an intellectual disability at five time points over 18 years. Data were examined from a total of 248 people with one of the four following syndromes: Down syndrome, Fragile X syndrome, Prader-Willi syndrome, or Williams syndrome. Changes in behaviors were measured using validated items from the Developmental Behavior Checklist (DBC). The results indicate that, while verbal aggression shows no evidence of diminishing with age, physical aggression, and temper tantrums decline with age before 19 years for people with Down syndrome, Fragile X syndrome, and William syndrome; and after 19 years for people with Prader-Willi syndrome. These findings offer a somewhat more optimistic outlook for people with an intellectual disability than has previously been suggested. Research is needed to investigate the mechanisms predisposing people with PWS to persistence of temper tantrums and physical aggression into adulthood. © 2015 Wiley Periodicals, Inc.

Investigation of Demodex folliculorum frequency in patients with polycystic ovary syndrome.

PubMed

Eser, Ayla; Erpolat, Seval; Kaygusuz, Ikbal; Balci, Hatice; Kosus, Aydin

2017-01-01

Background: Demodex mites are acari that reside in the pilosebaceous unit of the skin and have been associated with skin disorders. The objective of this study was to investigate the prevalence of Demodex folliculorum (D. folliculorum) mites in polycystic ovary syndrome patients as well as to examine the relationship between Demodex infestation and the presence of acne and oily or dry skin types in polycystic ovary syndrome patients. 41 polycystic ovary syndrome patients and 47 non-polycystic ovary syndrome control subjects were enrolled in the study. polycystic ovary syndrome was diagnosed according to the revised 2003 ESHRE/ASRM polycystic ovary syndrome Consensus Workshop Group diagnostic criteria. Microscopic examination of D. folliculorum mites was carried out by standardized skin surface biopsy. The result was considered positive when there were more than 5 mites per cm2. D. folliculorum was positive in 53.7% of the polycystic ovary syndrome patients and 31.9% of the non-polycystic ovary syndrome group (p=0.052). Demodex positivity was significantly associated with acne (p=0.003) and oily skin (p=0.005) in the polycystic ovary syndrome patients but not in the controls. Our study is limited by the relatively small number of subjects and the observational nature of the study design. Demodex mites might have a role in acne pathogenesis in patients with polycystic ovary syndrome. Anti-Demodex treatment may increase the response to treatment of acne. Further studies are indicated.

Phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in hyperinsulinemic db/db mice.

PubMed

Nishida, Hidenori; Sohara, Eisei; Nomura, Naohiro; Chiga, Motoko; Alessi, Dario R; Rai, Tatemitsu; Sasaki, Sei; Uchida, Shinichi

2012-10-01

Metabolic syndrome patients have insulin resistance, which causes hyperinsulinemia, which in turn causes aberrant increased renal sodium reabsorption. The precise mechanisms underlying this greater salt sensitivity of hyperinsulinemic patients remain unclear. Abnormal activation of the recently identified with-no-lysine kinase (WNK)-oxidative stress-responsive kinase 1 (OSR1)/STE20/SPS1-related proline/alanine-rich kinase (SPAK)-NaCl cotransporter (NCC) phosphorylation cascade results in the salt-sensitive hypertension of pseudohypoaldosteronism type II. Here, we report a study of renal WNK-OSR1/SPAK-NCC cascade activation in the db/db mouse model of hyperinsulinemic metabolic syndrome. Thiazide sensitivity was increased, suggesting greater activity of NCC in db/db mice. In fact, increased phosphorylation of OSR1/SPAK and NCC was observed. In both SpakT243A/+ and Osr1T185A/+ knock-in db/db mice, which carry mutations that disrupt the signal from WNK kinases, increased phosphorylation of NCC and elevated blood pressure were completely corrected, indicating that phosphorylation of SPAK and OSR1 by WNK kinases is required for the increased activation and phosphorylation of NCC in this model. Renal phosphorylated Akt was increased in db/db mice, suggesting that increased NCC phosphorylation is regulated by the phosphatidylinositol 3-kinase/Akt signaling cascade in the kidney in response to hyperinsulinemia. A phosphatidylinositol 3-kinase inhibitor (NVP-BEZ235) corrected the increased OSR1/SPAK-NCC phosphorylation. Another more specific phosphatidylinositol 3-kinase inhibitor (GDC-0941) and an Akt inhibitor (MK-2206) also inhibited increased NCC phosphorylation. These results indicate that the phosphatidylinositol 3-kinase/Akt signaling pathway activates the WNK-OSR1/SPAK-NCC phosphorylation cascade in db/db mice. This mechanism may play a role in the pathogenesis of salt-sensitive hypertension in human hyperinsulinemic conditions, such as the metabolic syndrome.

Mathematics learning disability in girls with Turner syndrome or fragile X syndrome.

PubMed

Murphy, Melissa M; Mazzocco, Michèle M M; Gerner, Gwendolyn; Henry, Anne E

2006-07-01

Two studies were carried out to examine the persistence (Study 1) and characteristics (Study 2) of mathematics learning disability (MLD) in girls with Turner syndrome or fragile X during the primary school years (ages 5-9 years). In Study 1, the rate of MLD for each syndrome group exceeded the rate observed in a grade-matched comparison group, although the likelihood of MLD persisting through the primary school years was comparable for all three groups. In Study 2, formal and informal math skills were compared across the syndrome groups, a normative group, and children from the normative group who had MLD. Few differences were observed between the Turner syndrome and normative groups. Despite having rote counting and number representation skills comparable to those in the normative group, girls with fragile X had difficulty with counting rules (e.g., cardinality, number constancy). However, this difficulty did not distingush them from the MLD group. Overall, counting skills appear to distinguish the Turner syndrome and fragile X groups, suggesting that the specificity of math deficits emerges earlier for fragile X than Turner syndrome.

Burnout syndrome in first to sixth-year medical students at a private university in the north of Mexico: descriptive cross-sectional study.

PubMed

Asencio-López, Laura; Almaraz-Celis, Guillermo Daniel; Carrillo Maciel, Vicente; Huerta Valenzuela, Paola; Silva Goytia, Luis; Muñoz Torres, Marcos; Monroy Caballero, Fernando; Regalado Tapia, Joel; Dipp Martin, Kerigma; López Miranda, Dinorah; Medina Lavenant, Clyvia; Pizarro Rodríguez, Karen; Santiago Martínez, Cesar; Saucedo Aparicio, Alma Geovanna; Flores Lepe, Rodolfo

2016-04-25

Burnout syndrome is a three-dimensional clinical syndrome caused by stress at work. It is frequent in professions which require direct contact with people. In Mexico, the presence of Burnout Syndrome in doctors and medical students, is characterized as a threat to their health, quality of life and professional performance. To evaluate the prevalence of burnout syndrome in students of years 1 through 6 of medical school at a private university in northern Mexico. Cross-sectional study in the Escuela de Medicina Campus Laguna de la Universidad Autónoma de Durango. The one-dimensional scale of Burnout Student (EUBE) and the Maslach Burnout Inventory (MBI) were applied to the participants. SPSS 19 was used to analyze the data. Of the 344 students, 255 participated; 153 from years 1 to 3 (group 1); and 72 from years 4 to 6 (group 2). We found that 94.1% of the students of group 1 had mild burnout syndrome, and 2.8% had moderate burnout syndrome. In Group 2, 27.8% had moderate burnout syndrome, and 8.3% had severe burnout syndrome. The prevalence of severe burnout syndrome was higher in group 2 than in group 1 (p=0.02). Burnout syndrome affects medical students across all stages of their studies, and develops in a progressive way. In our study, external factors have no influence on the development of burnout syndrome.

Basal cell nevus syndrome (Gorlin syndrome): genetic insights, diagnostic challenges, and unmet milestones.

PubMed

Akbari, Maryam; Chen, Harold; Guo, Grace; Legan, Zachary; Ghali, Ghali

2018-01-31

In this article, we present three clinical case reports on Basal Cell Nevus Syndrome (Gorlin Syndrome). Gorlin syndrome is an inherited medical condition with challenges that manifest in multiple body systems and complicate early diagnosis. We examine the epidemiology of the disease and benefits of genetic testing, molecular pathophysiology, and advancement in the molecular-based therapy of Basal Cell Nevus syndrome. The goal of this paper is to shed light on both unmet challenges and advancements in the management of Gorlin syndrome and to provide a new clinical perspective and guidance for future research. Furthermore, the FDA approved Hedgehog pathway inhibitors Vismodegib and Sonidegib designed for advanced basal cell carcinoma have opened a new door for treatment that may ultimately decrease the number of surgeries for a patient with Gorlin syndrome. The role of these agents in syndromic odontogenic keratocyst has not been studied extensively, but one study found that hedgehog pathway inhibitors decrease the size of syndromic odontogenic keratocyst. Ideal surgical treatment that balances low recurrence rates with low impact on one's quality of life for syndromic odontogenic keratocyst is another unanswered question for oral and maxillofacial surgeons. Per survey studies, treatment options practiced for syndromic odontogenic keratocyst range from marsupialization to segmental osteotomy. Future studies performed should take a comprehensive long-term approach with at least three years of follow-up in order to determine the most appropriate treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

Independent associations between a metabolic syndrome severity score and future diabetes by sex and race: the Atherosclerosis Risk In Communities Study and Jackson Heart Study.

PubMed

Gurka, Matthew J; Golden, Sherita H; Musani, Solomon K; Sims, Mario; Vishnu, Abhishek; Guo, Yi; Cardel, Michelle; Pearson, Thomas A; DeBoer, Mark D

2017-07-01

The study aimed to assess for an association between the degree of severity of the metabolic syndrome and risk of type 2 diabetes beyond that conferred by the individual components of the metabolic syndrome. We assessed HRs for an Adult Treatment Panel III (ATP-III) metabolic syndrome score (ATP-III MetS) and a sex- and race-specific continuous metabolic syndrome severity z score related to incident diabetes over a median of 7.8 years of follow-up among participants of two observational cohorts, the Atherosclerosis Risk in Communities study (n = 10,957) and the Jackson Heart Study (n = 2137). The ATP-III MetS had an HR for incident diabetes of 4.36 (95% CI 3.83, 4.97), which was attenuated in models that included the individual metabolic syndrome components. By contrast, participants in the fourth quartile of metabolic syndrome severity (compared with the first quartile) had an HR of 17.4 (95% CI 12.6, 24.1) for future diabetes; in models that also included the individual metabolic syndrome components, this remained significant, with an HR of 3.69 (95% CI 2.42, 5.64). There was a race × metabolic syndrome interaction in these models such that HR was greater for black participants (5.30) than white participants (2.24). When the change in metabolic syndrome severity score was included in the hazard models, this conferred a further association, with changes in metabolic syndrome severity score of ≥0.5 having a HR of 2.66 compared with changes in metabolic syndrome severity score of ≤0. Use of a continuous sex- and race-specific metabolic syndrome severity z score provided an additional prediction of risk of diabetes beyond that of the individual metabolic syndrome components, suggesting an added risk conferred by the processes underlying the metabolic syndrome. Increases in this score over time were associated with further risk, supporting the potential clinical utility of following metabolic syndrome severity over time.

[Clinical study of area of Jiangsu province of polycystic ovarian syndrome correlation distribution of traditional Chinese medicine syndrome type and improper diet].

PubMed

Feng, Yu; Gao, Yue-Ping

2014-05-01

Polycystic ovary syndrome (PCOS) is one of the most popular diseases in obstetrics and gynecology research at internal and abroad at present, traditional Chinese medicine(TCM)in the clinical treatment of the disease have the advantage. Clinical epidemiological study of descriptive research method this research adopts investigation, observation of TCM syndromes and improper diet through 401 cases in Jiangsu Province confirmed PCOS patients, to explore the relationship between TCM syndrome type distribution and improper diet factors, and to provide the clinical basis for further etiology of this disease research. TCM syndrome type distribution of the disease is kidney deficiency, phlegm stagnation syndrome, qi stagnation and blood stasis syndrome, syndrome of dampness heat of liver channel and is composed of 4 basic syndromes and formed complex syndrome, and the composite and syndrome type (60.85%); combined with the analysis of traditional Chinese medicine dialectical, Pure empirical syndrome this disease (46.88%), followed by the actual card (45.39%), pure deficiency is rare. Improper diet factors associated with the disease, in which improper diet with different TCM syndrome type distribution significantly related. Stagnation of phlegm dampness syndrome is the main syndrome of the disease type, improper diet factors and every syndrome PCOS type distribution is as follows: the partial eclipse fatness greasy with basic syndromes of phlegm dampness stagnation of kidney deficiency syndrome, the nephrasthenia syndrome is less; eating spicy stimulation by basic syndromes of stagnation of Qi and blood stasis; eating cold people the basic certificate type of qi stagnation and blood stasis; The diet of patients are more prone to stagnation of phlegm dampness syndrome.

Cohort profile of BIOMArCS: the BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands.

PubMed

Oemrawsingh, Rohit M; Akkerhuis, K Martijn; Umans, Victor A; Kietselaer, Bas; Schotborgh, Carl; Ronner, Eelko; Lenderink, Timo; Liem, Anho; Haitsma, David; van der Harst, Pim; Asselbergs, Folkert W; Maas, Arthur; Oude Ophuis, Anton J; Ilmer, Ben; Dijkgraaf, Rene; de Winter, Robbert-Jan; The, S Hong Kie; Wardeh, Alexander J; Hermans, Walter; Cramer, Etienne; van Schaik, Ron H; Hoefer, Imo E; Doevendans, Pieter A; Simoons, Maarten L; Boersma, Eric

2016-12-23

Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for non-fatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS. Follow-up and event adjudication have been completed. Prespecified biomarker analyses are currently being performed and dissemination through peer-reviewed publications and conference presentations is expected from the third quarter of 2016. Should identification of a 'vulnerable period' prove to be feasible, then future research could focus on event reduction through pharmacological or mechanical intervention during such periods of high risk for ACS. NTR1698 and NTR1106. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prevalence of metabolic syndrome and cardiovascular risk level in a vulnerable population.

PubMed

Kim, Chun-Ja; Park, JeeWon; Kang, Se-Won

2015-04-01

This study examined the prevalence of metabolic syndrome and the risk level of cardiovascular disease (CVD) in a vulnerable population of 407 subjects in Korea. This descriptive study was a part of the Tailed Health Visiting Service Program, using baseline data from public health centres in Suwon, Korea. The definition of metabolic syndrome was based on the National Cholesterol Education Program criteria, and risk of CVD was estimated according to the Framingham study equation. This study demonstrated that the prevalence of metabolic syndrome was 40.8% higher and the risk of CVD was significantly 3.1 times higher among those with metabolic syndrome than among those without it. Of those with metabolic syndrome, 50.6% overall and 81.1% of men had a high risk for CVD. These findings suggest a need to screen and prevent the risk of CVD in vulnerable populations with metabolic syndrome. © 2014 Wiley Publishing Asia Pty Ltd.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease.

PubMed

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas ( e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang ). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses.

Integrated Modules Analysis to Explore the Molecular Mechanisms of Phlegm-Stasis Cementation Syndrome with Ischemic Heart Disease

PubMed Central

Xu, Wei-Ming; Yang, Kuo; Jiang, Li-Jie; Hu, Jing-Qing; Zhou, Xue-Zhong

2018-01-01

Background: Ischemic heart disease (IHD) has been the leading cause of death for several decades globally, IHD patients usually hold the symptoms of phlegm-stasis cementation syndrome (PSCS) as significant complications. However, the underlying molecular mechanisms of PSCS complicated with IHD have not yet been fully elucidated. Materials and Methods: Network medicine methods were utilized to elucidate the underlying molecular mechanisms of IHD phenotypes. Firstly, high-quality IHD-associated genes from both human curated disease-gene association database and biomedical literatures were integrated. Secondly, the IHD disease modules were obtained by dissecting the protein-protein interaction (PPI) topological modules in the String V9.1 database and the mapping of IHD-associated genes to the PPI topological modules. After that, molecular functional analyses (e.g., Gene Ontology and pathway enrichment analyses) for these IHD disease modules were conducted. Finally, the PSCS syndrome modules were identified by mapping the PSCS related symptom-genes to the IHD disease modules, which were further validated by both pharmacological and physiological evidences derived from published literatures. Results: The total of 1,056 high-quality IHD-associated genes were integrated and evaluated. In addition, eight IHD disease modules (the PPI sub-networks significantly relevant to IHD) were identified, in which two disease modules were relevant to PSCS syndrome (i.e., two PSCS syndrome modules). These two modules had enriched pathways on Toll-like receptor signaling pathway (hsa04620) and Renin-angiotensin system (hsa04614), with the molecular functions of angiotensin maturation (GO:0002003) and response to bacterium (GO:0009617), which had been validated by classical Chinese herbal formulas-related targets, IHD-related drug targets, and the phenotype features derived from human phenotype ontology (HPO) and published biomedical literatures. Conclusion: A network medicine-based approach was proposed to identify the underlying molecular modules of PSCS complicated with IHD, which could be used for interpreting the pharmacological mechanisms of well-established Chinese herbal formulas (e.g., Tao Hong Si Wu Tang, Dan Shen Yin, Hunag Lian Wen Dan Tang and Gua Lou Xie Bai Ban Xia Tang). In addition, these results delivered novel understandings of the molecular network mechanisms of IHD phenotype subtypes with PSCS complications, which would be both insightful for IHD precision medicine and the integration of disease and TCM syndrome diagnoses. PMID:29403392

Lesion correlates of patholinguistic profiles in chronic aphasia: comparisons of syndrome-, modality- and symptom-level assessment.

PubMed

Henseler, Ilona; Regenbrecht, Frank; Obrig, Hellmuth

2014-03-01

One way to investigate the neuronal underpinnings of language competence is to correlate patholinguistic profiles of aphasic patients to corresponding lesion sites. Constituting the beginnings of aphasiology and neurolinguistics over a century ago, this approach has been revived and refined in the past decade by statistical approaches mapping continuous variables (providing metrics that are not simply categorical) on voxel-wise lesion information (voxel-based lesion-symptom mapping). Here we investigate whether and how voxel-based lesion-symptom mapping allows us to delineate specific lesion patterns for differentially fine-grained clinical classifications. The latter encompass 'classical' syndrome-based approaches (e.g. Broca's aphasia), more symptom-oriented descriptions (e.g. agrammatism) and further refinement to linguistic sub-functions (e.g. lexico-semantic deficits for inanimate versus animate items). From a large database of patients treated for aphasia of different aetiologies (n = 1167) a carefully selected group of 102 first ever ischaemic stroke patients with chronic aphasia (∅ 12 months) were included in a VLSM analysis. Specifically, we investigated how performance in the Aachen Aphasia Test-the standard clinical test battery for chronic aphasia in German-relates to distinct brain lesions. The Aachen Aphasia Test evaluates aphasia on different levels: a non-parametric discriminant procedure yields probabilities for the allocation to one of the four 'standard' syndromes (Broca, Wernicke, global and amnestic aphasia), whereas standardized subtests target linguistic modalities (e.g. repetition), or even more specific symptoms (e.g. phoneme repetition). Because some subtests of the Aachen Aphasia Test (e.g. for the linguistic level of lexico-semantics) rely on rather coarse and heterogeneous test items we complemented the analysis with a number of more detailed clinically used tests in selected mostly mildly affected subgroups of patients. Our results indicate that: (i) Aachen Aphasia Test-based syndrome allocation allows for an unexpectedly concise differentiation between 'Broca's' and 'Wernicke's' aphasia corresponding to non-overlapping anterior and posterior lesion sites; whereas (ii) analyses for modalities and specific symptoms yielded more circumscribed but partially overlapping lesion foci, often cutting across the above syndrome territories; and (iii) especially for lexico-semantic capacities more specialized clinical test-batteries are required to delineate precise lesion patterns at this linguistic level. In sum this is the first report on a successful lesion-delineation of syndrome-based aphasia classification highlighting the relevance of vascular distribution for the syndrome level while confirming and extending a number of more linguistically motivated differentiations, based on clinically used tests. We consider such a comprehensive view reaching from the syndrome to a fine-grained symptom-oriented assessment mandatory to converge neurolinguistic, patholinguistic and clinical-therapeutic knowledge on language-competence and impairment.

Incremental Predictive Value of Serum AST-to-ALT Ratio for Incident Metabolic Syndrome: The ARIRANG Study

PubMed Central

Ahn, Song Vogue; Baik, Soon Koo; Cho, Youn zoo; Koh, Sang Baek; Huh, Ji Hye; Chang, Yoosoo; Sung, Ki-Chul; Kim, Jang Young

2016-01-01

Aims The ratio of aspartate aminotransferase (AST) to alanine aminotransferase (ALT) is of great interest as a possible novel marker of metabolic syndrome. However, longitudinal studies emphasizing the incremental predictive value of the AST-to-ALT ratio in diagnosing individuals at higher risk of developing metabolic syndrome are very scarce. Therefore, our study aimed to evaluate the AST-to-ALT ratio as an incremental predictor of new onset metabolic syndrome in a population-based cohort study. Material and Methods The population-based cohort study included 2276 adults (903 men and 1373 women) aged 40–70 years, who participated from 2005–2008 (baseline) without metabolic syndrome and were followed up from 2008–2011. Metabolic syndrome was defined according to the harmonized definition of metabolic syndrome. Serum concentrations of AST and ALT were determined by enzymatic methods. Results During an average follow-up period of 2.6-years, 395 individuals (17.4%) developed metabolic syndrome. In a multivariable adjusted model, the odds ratio (95% confidence interval) for new onset of metabolic syndrome, comparing the fourth quartile to the first quartile of the AST-to-ALT ratio, was 0.598 (0.422–0.853). The AST-to-ALT ratio also improved the area under the receiver operating characteristic curve (AUC) for predicting new cases of metabolic syndrome (0.715 vs. 0.732, P = 0.004). The net reclassification improvement of prediction models including the AST-to-ALT ratio was 0.23 (95% CI: 0.124–0.337, P<0.001), and the integrated discrimination improvement was 0.0094 (95% CI: 0.0046–0.0143, P<0.001). Conclusions The AST-to-ALT ratio independently predicted the future development of metabolic syndrome and had incremental predictive value for incident metabolic syndrome. PMID:27560931

In vivo tear film thickness measurement and tear film dynamics visualization using spectral domain OCT and an efficient delay estimator

NASA Astrophysics Data System (ADS)

Aranha dos Santos, Valentin; Schmetterer, Leopold; Gröschl, Martin; Garhofer, Gerhard; Werkmeister, René M.

2016-03-01

Dry eye syndrome is a highly prevalent disease of the ocular surface characterized by an instability of the tear film. Traditional methods used for the evaluation of tear film stability are invasive or show limited repeatability. Here we propose a new noninvasive approach to measure tear film thickness using an efficient delay estimator and ultrahigh resolution spectral domain OCT. Silicon wafer phantoms with layers of known thickness and group index were used to validate the estimator-based thickness measurement. A theoretical analysis of the fundamental limit of the precision of the estimator is presented and the analytical expression of the Cramér-Rao lower bound (CRLB), which is the minimum variance that may be achieved by any unbiased estimator, is derived. The performance of the estimator against noise was investigated using simulations. We found that the proposed estimator reaches the CRLB associated with the OCT amplitude signal. The technique was applied in vivo in healthy subjects and dry eye patients. Series of tear film thickness maps were generated, allowing for the visualization of tear film dynamics. Our results show that the central tear film thickness precisely measured in vivo with a coefficient of variation of about 0.65% and that repeatable tear film dynamics can be observed. The presented method has the potential of being an alternative to breakup time measurements (BUT) and could be used in clinical setting to study patients with dry eye disease and monitor their treatments.

What is going on between defibrotide and endothelial cells? Snapshots reveal the hot spots of their romance

PubMed Central

Mir, Enrique; Rovira, Montse; Escolar, Ginés; Carreras, Enric; Diaz-Ricart, Maribel

2016-01-01

Defibrotide (DF) has received European Medicines Agency authorization to treat sinusoidal obstruction syndrome, an early complication after hematopoietic cell transplantation. DF has a recognized role as an endothelial protective agent, although its precise mechanism of action remains to be elucidated. The aim of the present study was to investigate the interaction of DF with endothelial cells (ECs). A human hepatic EC line was exposed to different DF concentrations, previously labeled. Using inhibitory assays and flow cytometry techniques along with confocal microscopy, we explored: DF-EC interaction, endocytic pathways, and internalization kinetics. Moreover, we evaluated the potential role of adenosine receptors in DF-EC interaction and if DF effects on endothelium were dependent of its internalization. Confocal microscopy showed interaction of DF with EC membranes followed by internalization, though DF did not reach the cell nucleus even after 24 hours. Flow cytometry revealed concentration, temperature, and time dependent uptake of DF in 2 EC models but not in other cell types. Moreover, inhibitory assays indicated that entrance of DF into ECs occurs primarily through macropinocytosis. Our experimental approach did not show any evidence of the involvement of adenosine receptors in DF-EC interaction. The antiinflammatory and antioxidant properties of DF seem to be caused by the interaction of the drug with the cell membrane. Our findings contribute to a better understanding of the precise mechanisms of action of DF as a therapeutic and potential preventive agent on the endothelial damage underlying different pathologic situations. PMID:26755708

Automated brain volumetrics in multiple sclerosis: a step closer to clinical application.

PubMed

Wang, C; Beadnall, H N; Hatton, S N; Bader, G; Tomic, D; Silva, D G; Barnett, M H

2016-07-01

Whole brain volume (WBV) estimates in patients with multiple sclerosis (MS) correlate more robustly with clinical disability than traditional, lesion-based metrics. Numerous algorithms to measure WBV have been developed over the past two decades. We compare Structural Image Evaluation using Normalisation of Atrophy-Cross-sectional (SIENAX) to NeuroQuant and MSmetrix, for assessment of cross-sectional WBV in patients with MS. MRIs from 61 patients with relapsing-remitting MS and 2 patients with clinically isolated syndrome were analysed. WBV measurements were calculated using SIENAX, NeuroQuant and MSmetrix. Statistical agreement between the methods was evaluated using linear regression and Bland-Altman plots. Precision and accuracy of WBV measurement was calculated for (1) NeuroQuant versus SIENAX and (2) MSmetrix versus SIENAX. Precision (Pearson's r) of WBV estimation for NeuroQuant and MSmetrix versus SIENAX was 0.983 and 0.992, respectively. Accuracy (Cb) was 0.871 and 0.994, respectively. NeuroQuant and MSmetrix showed a 5.5% and 1.0% volume difference compared with SIENAX, respectively, that was consistent across low and high values. In the analysed population, NeuroQuant and MSmetrix both quantified cross-sectional WBV with comparable statistical agreement to SIENAX, a well-validated cross-sectional tool that has been used extensively in MS clinical studies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The use of syndromic surveillance for decision-making during the H1N1 pandemic: a qualitative study.

PubMed

Chu, Anna; Savage, Rachel; Willison, Don; Crowcroft, Natasha S; Rosella, Laura C; Sider, Doug; Garay, Jason; Gemmill, Ian; Winter, Anne-Luise; Davies, Richard F; Johnson, Ian

2012-10-30

Although an increasing number of studies are documenting uses of syndromic surveillance by front line public health, few detail the value added from linking syndromic data to public health decision-making. This study seeks to understand how syndromic data informed specific public health actions during the 2009 H1N1 pandemic. Semi-structured telephone interviews were conducted with participants from Ontario's public health departments, the provincial ministry of health and federal public health agency to gather information about syndromic surveillance systems used and the role of syndromic data in informing specific public health actions taken during the pandemic. Responses were compared with how the same decisions were made by non-syndromic surveillance users. Findings from 56 interviews (82% response) show that syndromic data were most used for monitoring virus activity, measuring impact on the health care system and informing the opening of influenza assessment centres in several jurisdictions, and supporting communications and messaging, rather than its intended purpose of early outbreak detection. Syndromic data had limited impact on decisions that involved the operation of immunization clinics, school closures, sending information letters home with school children or providing recommendations to health care providers. Both syndromic surveillance users and non-users reported that guidance from the provincial ministry of health, communications with stakeholders and vaccine availability were driving factors in these public health decisions. Syndromic surveillance had limited use in decision-making during the 2009 H1N1 pandemic in Ontario. This study provides insights into the reasons why this occurred. Despite this, syndromic data were valued for providing situational awareness and confidence to support public communications and recommendations. Developing an understanding of how syndromic data are utilized during public health events provides valuable evidence to support future investments in public health surveillance.

Clinical characteristics of metabolic syndrome in Korea, and its comparison with other Asian countries.

PubMed

Hong, A Ram; Lim, Soo

2015-09-01

Metabolic syndrome is referred to as syndrome X or insulin resistance syndrome, and is primarily composed of abdominal obesity, diabetes, glucose intolerance, dyslipidemia and high blood pressure. Asians have a lower frequency of obesity than Caucasians, but have an increasing tendency toward metabolic syndrome. Thus, metabolic syndrome poses a major challenge for public health professionals, and is set to become a social and economic problem in Asian populations. Most data on metabolic syndrome are based on studies from Western countries with only limited information derived from Asian populations. Recently, several studies were carried out on a large scale that represents the general Korean population. The prevalence of metabolic syndrome in Korean adults has varied depending on the study designs and different criteria, but shows a distinct increasing trend of metabolic syndrome driven by an increase in abdominal obesity and dyslipidemia. Given the rapid economic progression of Korea over the past 30 years along with a rise of the aged population, it is expected that the prevalence of metabolic syndrome will further increase. Therefore, a proactive strategy at the governmental level for metabolic syndrome prevention should be implemented, reducing abdominal obesity and dyslipidemia. Healthy dietary habits and regular exercise should be emphasized as a part of such a strategy.

Clinical characteristics of metabolic syndrome in Korea, and its comparison with other Asian countries

PubMed Central

Hong, A Ram; Lim, Soo

2015-01-01

Metabolic syndrome is referred to as syndrome X or insulin resistance syndrome, and is primarily composed of abdominal obesity, diabetes, glucose intolerance, dyslipidemia and high blood pressure. Asians have a lower frequency of obesity than Caucasians, but have an increasing tendency toward metabolic syndrome. Thus, metabolic syndrome poses a major challenge for public health professionals, and is set to become a social and economic problem in Asian populations. Most data on metabolic syndrome are based on studies from Western countries with only limited information derived from Asian populations. Recently, several studies were carried out on a large scale that represents the general Korean population. The prevalence of metabolic syndrome in Korean adults has varied depending on the study designs and different criteria, but shows a distinct increasing trend of metabolic syndrome driven by an increase in abdominal obesity and dyslipidemia. Given the rapid economic progression of Korea over the past 30 years along with a rise of the aged population, it is expected that the prevalence of metabolic syndrome will further increase. Therefore, a proactive strategy at the governmental level for metabolic syndrome prevention should be implemented, reducing abdominal obesity and dyslipidemia. Healthy dietary habits and regular exercise should be emphasized as a part of such a strategy. PMID:26417407

Neuropsychiatric symptoms and syndromes in a large cohort of newly diagnosed, untreated patients with Alzheimer disease.

PubMed

Spalletta, Gianfranco; Musicco, Massimo; Padovani, Alesandro; Rozzini, Luca; Perri, Roberta; Fadda, Lucia; Canonico, Vincenzo; Trequattrini, Alberto; Pettenati, Carla; Caltagirone, Carlo; Palmer, Katie

2010-11-01

Neuropsychiatric symptoms are common in patients with Alzheimer disease (AD). Treatment for both AD and psychiatric disturbances may affect the clinical observed pattern and comorbidity. The authors aimed to identify whether particular neuropsychiatric syndromes occur in untreated patients with AD, establish the severity of syndromes, and investigate the relationship between specific neuropsychiatric syndromes and AD disease severity. Cross-sectional, multicenter, clinical study. A total of 1,015 newly diagnosed, untreated outpatients with AD from five Italian memory clinics were consecutively enrolled in the study from January 2003 to December 2005. All patients underwent thorough examination by clinical neurologists/geriatricians, including neuropsychiatric symptom evaluation with the Neuropsychiatric Inventory. Factor analysis revealed five distinct neuropsychiatric syndromes: the apathetic syndrome (as unique syndrome) was the most frequent, followed by affective syndrome (anxiety and depression), psychomotor (agitation, irritability, and aberrant motor behavior), psychotic (delusions and hallucinations), and manic (disinhibition and euphoria) syndromes. More than three quarters of patients with AD presented with one or more of the syndromes (N = 790, 77.8%), and more than half exhibited clinically significant severity of symptoms (N = 603, 59.4%). With the exception of the affective one, all syndromes showed an increased occurrence with increasing severity of dementia. The authors' study supports the use of a syndrome approach for neuropsychiatric evaluation in patients with AD. Individual neuropsychiatric symptoms can be reclassified into five distinct psychiatric syndromes. Clinicians should incorporate a thorough psychiatric and neurologic examination of patients with AD and consider therapeutic strategies that focus on psychiatric syndromes, rather than specific individual symptoms.

Survey Study and Records Review of Treatment Outcomes in Freeman-Sheldon Syndrome

ClinicalTrials.gov

2018-03-30

Freeman-Sheldon Syndrome; Arthrogryposis Distal Type 2A; Whistling Face Syndrome; Craniocarpotarsal Dysplasia; Craniocarpotarsal Dystrophy; Freeman-Sheldon Syndrome Variant; Sheldon-Hall Syndrome; Arthrogryposis Distal Type 2B; Gordon Syndrome; Arthrogryposis Distal Type 3; Arthrogryposis Distal Type 1; Arthrogryposis, Distal, Type 1A; Arthrogryposis Distal Type 1B; Arthrogryposis, Distal; Craniofacial Abnormalities; Arthrogryposis

Numerical Magnitude Processing Impairments in Genetic Syndromes: A Cross-Syndrome Comparison of Turner and 22Q11.2 Deletion Syndromes

ERIC Educational Resources Information Center

Brankaer, Carmen; Ghesquière, Pol; De Wel, Anke; Swillen, Ann; De Smedt, Bert

2017-01-01

Cross-syndrome comparisons offer an important window onto understanding heterogeneity in mathematical learning disabilities or dyscalculia. The present study therefore investigated symbolic numerical magnitude processing in two genetic syndromes that are both characterized by mathematical learning disabilities: Turner syndrome and 22q11.2 deletion…

Esophageal Dysmotility, Gastro-esophageal Reflux Disease, and Lung Transplantation: What Is the Evidence?

PubMed

Wood, Richard K

2015-12-01

Lung transplantation is an effective and life-prolonging therapy for patients with advanced lung disease (ALD). However, long-term patient survival following lung transplantation is primarily limited by development of an inflammatory and fibrotic process involving the lung allograft known as bronchiolitis obliterans syndrome (BOS). Although the precise cause of BOS remains uncertain and is likely multifactorial, chronic aspiration of gastro-duodenal contents is one possible contributing factor. Multiple small, cross-sectional studies performed over the past two decades have reported a high prevalence of gastro-esophageal reflux disease (GERD) and esophageal dysmotility in the ALD population and several investigations suggest the prevalence may increase following lung transplantation. More recent studies evaluating the direct effect of gastro-duodenal contents on airways have demonstrated a possible biologic link between GERD and BOS. Despite the recent advances in our understanding of BOS, further investigations are needed to establish GERD as a causative factor in its development. This review will discuss the existing literature that has identified an association of GERD with ALD and post-transplant populations, with a focus on recent advances in the field.

SlgA, encoded by the homolog of the human schizophrenia-associated gene PRODH, acts in clock neurons to regulate Drosophila aggression.

PubMed

Zwarts, Liesbeth; Vulsteke, Veerle; Buhl, Edgar; Hodge, James J L; Callaerts, Patrick

2017-06-01

Mutations in the proline dehydrogenase gene PRODH are linked to behavioral alterations in schizophrenia and as part of DiGeorge and velo-cardio-facial syndromes, but the role of PRODH in their etiology remains unclear. Here, we establish a Drosophila model to study the role of PRODH in behavioral disorders. We determine the distribution of the Drosophila PRODH homolog slgA in the brain and show that knockdown and overexpression of human PRODH and slgA in the lateral neurons ventral (LNv) lead to altered aggressive behavior. SlgA acts in an isoform-specific manner and is regulated by casein kinase II (CkII). Our data suggest that these effects are, at least partially, due to effects on mitochondrial function. We thus show that precise regulation of proline metabolism is essential to drive normal behavior and we identify Drosophila aggression as a model behavior relevant for the study of the mechanisms that are impaired in neuropsychiatric disorders. © 2017. Published by The Company of Biologists Ltd.

Music in disorders of consciousness.

PubMed

Rollnik, Jens D; Altenmüller, Eckart

2014-01-01

This review presents an overview of the use of music therapy in neurological early rehabilitation of patients with coma and other disorders of consciousness (DOC) such as unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). There is evidence that patients suffering from UWS show emotional processing of auditory information, such as listening to speech. Thus, it seems reasonable to believe that music listening-as part of an enriched environment setting-may be of therapeutic value in these patients. There is, however, a considerable lack of evidence. The authors strongly encourage further studies to evaluate the efficacy of music listening in patients with DOC in neurological early rehabilitation. These studies should consider a precise clinical definition and homogeneity of the patient cohort with respect to the quality (coma vs. UWS vs. MCS), duration (rather weeks to months than days) and cause (traumatic vs. non-traumatic) of DOC, a standardized intervention protocol, valid clinical outcome parameters over a longer observation period (weeks to months), monitoring of neurophysiological and vegetative parameters and, if available, neuroimaging to confirm diagnosis and to demonstrate responses and functional changes in the patients' brains.

Music in disorders of consciousness

PubMed Central

Rollnik, Jens D.; Altenmüller, Eckart

2014-01-01

This review presents an overview of the use of music therapy in neurological early rehabilitation of patients with coma and other disorders of consciousness (DOC) such as unresponsive wakefulness syndrome (UWS) or minimally conscious state (MCS). There is evidence that patients suffering from UWS show emotional processing of auditory information, such as listening to speech. Thus, it seems reasonable to believe that music listening—as part of an enriched environment setting—may be of therapeutic value in these patients. There is, however, a considerable lack of evidence. The authors strongly encourage further studies to evaluate the efficacy of music listening in patients with DOC in neurological early rehabilitation. These studies should consider a precise clinical definition and homogeneity of the patient cohort with respect to the quality (coma vs. UWS vs. MCS), duration (rather weeks to months than days) and cause (traumatic vs. non-traumatic) of DOC, a standardized intervention protocol, valid clinical outcome parameters over a longer observation period (weeks to months), monitoring of neurophysiological and vegetative parameters and, if available, neuroimaging to confirm diagnosis and to demonstrate responses and functional changes in the patients' brains. PMID:25071434

A comparative study of educational provision for children with neurogenetic syndromes: parent and teacher survey.

PubMed

Reilly, C; Senior, J; Murtagh, L

2015-12-01

A number of neurogenetic syndromes have a high association with special educational needs including fragile X syndrome (FXS), Prader-Willi syndrome (PWS), Williams syndrome (WS) and Velo-Cardio-Facial syndrome (VCFS). There is a paucity of research on educational provision for children affected by these syndromes. Parents (n = 381) and teachers (n = 204) of school-aged children with one of the four syndromes in the UK and Ireland were surveyed in a range of areas concerning the child's educational provision. Areas surveyed included school placement, views on the needs of children with the syndromes, desired changes to current provision and perceived teacher knowledge. School placement in mainstream settings decreased with age in all of the syndromes. Males with the syndromes were more likely to be in specialised educational settings with the exception of WS. Teachers reported limited input on initial or subsequent training for all of the syndromes. The majority of teachers did not view the needs of children with syndromes as different from other children with intellectual disability (ID) although there were significant differences between the syndromes. Changes deemed necessary to provision by parents and teachers differed between the syndromes indicating the existence of perceptions of syndrome specific needs. The lowest perceived level of teacher knowledge was in the VCFS group. The majority of teachers of children with neurogenetic syndromes report limited knowledge of the syndromes, but also a lack of belief that the children's needs are different from the majority of children with ID. Differences between the syndromes in some areas of provision suggest that a child's syndrome does impact on educational provision in some areas. © 2015 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

A Longitudinal Follow-Up Study of Affect in Children and Adults with Cornelia de Lange Syndrome

ERIC Educational Resources Information Center

Nelson, Lisa; Moss, Jo; Oliver, Chris

2014-01-01

Studies of individuals with Cornelia de Lange syndrome (CdLS) have described changes in mood and behavior with age, although no empirical or longitudinal studies have been conducted. Caregivers of individuals with CdLS (N = 67), cri du chat syndrome (CdCS; N = 42), and Fragile X syndrome (FXS; N = 142) completed the Mood, Interest and Pleasure…

[Significance and necessity of developing quality of life questionnaire for cancer patients adapting to traditional Chinese medicine].

PubMed

You, Jie

2006-09-01

The clinical evaluation system for therapeutic effects of tumor, which focuses on survival period and tumor response rate, has been proved not very proper for evaluating the therapeutic effects of traditional Chinese medicine (TCM). Quality of life (QOL) has been introduced into the effective evaluation system of TCM and integrative medicine because of its similarity in concept and extension with TCM at theory basis, syndrome differentiation-treatment, and evaluation of therapeutic effects. But there are no QOL questionnaires which can evaluate the therapeutic effects of TCM and integrative medicine precisely. This article discussed the necessity and significance of developing QOL questionnaire special for TCM.

Objective monitoring of mTOR inhibitor therapy by three-dimensional facial analysis.

PubMed

Baynam, Gareth S; Walters, Mark; Dawkins, Hugh; Bellgard, Matthew; Halbert, Anne R; Claes, Peter

2013-08-01

With advances in therapeutics for rare, genetic and syndromic diseases, there is an increasing need for objective assessments of phenotypic endpoints. These assessments will preferentially be high precision, non-invasive, non-irradiating, and relatively inexpensive and portable. We report a case of a child with an extensive lymphatic vascular malformation of the head and neck, treated with an mammalian target of Rapamycin (mTOR) inhibitor that was assessed using 3D facial analysis. This case illustrates that this technology is prospectively a cost-effective modality for treatment monitoring, and it supports that it may also be used for novel explorations of disease biology for conditions associated with disturbances in the mTOR, and interrelated, pathways.

Clinical presentations and phenomenology of myoclonus.

PubMed

Faught, Edward

2003-01-01

The term "myoclonus" has been used to describe heterogeneous phenomena involving sudden movements, but there is no generally accepted, precise definition of myoclonus. Myoclonus can often be classified based on electroencephalographic (EEG) and/or electromyographic (EMG) data. Some myoclonic epilepsy syndromes, including juvenile myoclonic epilepsy, may frequently be misdiagnosed because of failure to obtain a complete patient history and/or failure to appreciate characteristic EEG changes. A good understanding of the features associated with myoclonic disorders (particularly the myoclonic epilepsies) and of features associated with other neurologic disorders that are often confused with myoclonic disorders is an invaluable aid in obtaining an accurate diagnosis and will ultimately help in determining the best course of treatment for patients.

[Occupation-specific illnesses in musicians].

PubMed

Schuppert, M; Altenmüller, E

1999-12-01

Performance-related disorders in musicians are most often caused by multiple risk factors. They are based on the chronic complex, rapid and forceful work that requires highest precision, as well as on poor ergonomic conditions and psychological strain. Predominantly, the musculo-skeletal system of the upper extremity and the spine is affected by acute or chronic pain syndromes and neurological disorders. Stage fright and psychological tension frequently generate somatoform disorders and may contribute to the chronification of physical disabilities in musicians. Depending on the individual characteristics, the actual professional activity and the specific instrument, the performance-related risk factors and disorders differ widely. Early and regular prevention clearly contributes to a reduction of medical problems in musicians.

Airway Reflux, Cough and Respiratory Disease

PubMed Central

Molyneux, Ian D.; Morice, Alyn H.

2011-01-01

It is increasingly accepted that the effects of gastro-oesophageal reflux are not limited to the gastrointestinal tract. The adjacent respiratory structures are also at risk from material ejected from the proximal oesophagus as a result of the failure of anatomical and physiological barriers. There is evidence of the influence of reflux on several respiratory and otorhinological conditions and although in many cases the precise mechanism has yet to be elucidated, the association alone opens potential novel avenues of therapy to clinicians struggling to treat patients with apparently intractable respiratory complaints. This review provides a description of the airway reflux syndrome, its effects on the lung and current and future therapeutic options. PMID:23251752

What ailed Goya?

PubMed

Ravin, J G; Ravin, T B

1999-01-01

At age 46, Francisco de Goya (1746-1828) suffered from a severe illness that lasted several months. It caused loss of vision and hearing, tinnitus, disorientation, weakness, abdominal distress, and general malaise. After a few months he recuperated but was left deaf forever. In addition to the physical effects, his emotional health and artwork were affected. The precise cause of this illness has long been debated. One early, but unlikely, hypothesis was that he had syphilis. Later conjectures have included Vogt-Koyanagi-Harada disease and lead toxicity. Cogan's syndrome and vasculitis are additional possibilities, although neither is likely to have been Goya's diagnosis. An infectious disease such as meningitis, encephalitis, or malaria is far more likely. Quinine toxicity (cinchonism) may have complicated the illness.

Adaptive Servo-Ventilation in "Real Life" Conditions : the OTRLASV Study

ClinicalTrials.gov

2017-03-27

Chronic Heart Failure and; Complex Sleep Apnea Syndrome; Obstructive Sleep Apnea Syndrome and; Idiopathic Central Sleep Apnea Syndrome; Idiopathic Induced Periodic Breathing; Central Sleep Apnea Syndrome

Depression and Dementia in Aging Adults with Down Syndrome: A Case Study Approach.

ERIC Educational Resources Information Center

Sung, Hyunsook; And Others

1997-01-01

A case study of three adults (ages 46-47) with Down syndrome investigated the patterns of symptoms associated with depression and dementia. Characteristics that distinguish between dementia and depression in adults with Down syndrome are described. Periodic comprehensive assessment of adults with Down syndrome to detect functioning changes is…

Brief Report: Repetitive Behaviour Profiles in Williams syndrome: Cross Syndrome Comparisons with Prader-Willi and Down syndromes.

PubMed

Royston, R; Oliver, C; Moss, J; Adams, D; Berg, K; Burbidge, C; Howlin, P; Nelson, L; Stinton, C; Waite, J

2018-01-01

This study describes the profile of repetitive behaviour in individuals with Williams syndrome, utilising cross-syndrome comparisons with people with Prader-Willi and Down syndromes. The Repetitive Behaviour Questionnaire was administered to caregivers of adults with Williams (n = 96), Prader-Willi (n = 103) and Down (n = 78) syndromes. There were few group differences, although participants with Williams syndrome were more likely to show body stereotypies. Individuals with Williams syndrome also showed more hoarding and less tidying behaviours than those with Down syndrome. IQ and adaptive ability were negatively associated with repetitive questioning in people with Williams syndrome. The profile of repetitive behaviour amongst individuals with Williams syndrome was similar to the comparison syndromes. The cognitive mechanisms underlying these behaviours in genetic syndromes warrant further investigation.

Excess Metabolic Syndrome Risks Among Women Health Workers Compared With Men.

PubMed

Adeoye, Abiodun M; Adewoye, Ifeoluwa A; Dairo, David M; Adebiyi, Adewole; Lackland, Daniel T; Ogedegbe, Gbenga; Tayo, Bamidele O

2015-11-01

Metabolic syndrome is associated with higher rates of cardiovascular morbidity and mortality. Although significant disparities in the risks of metabolic syndrome by occupation type and sex are well documented, the factors associated with metabolic syndrome in low- to middle-income countries remain unclear. These gaps in evidence identify the need for patterns of metabolic syndrome among hospital personnel of both sexes in Nigeria. A total of 256 hospital workers comprising 32.8% men were studied. The mean age of the participants was 42.03 ± 9.4 years. Using International Diabetic Federation criteria, the prevalence of metabolic syndrome was 24.2%. Women were substantially and significantly more likely to be identified with metabolic syndrome compared with men (34.9% vs 2.4%, respectively; P=.0001). This study identified metabolic syndrome among health workers with over one third of women with metabolic syndrome compared with <10% of men. These results support the implementation of lifestyle modification programs for management of metabolic syndrome in the health care workplace. © 2015 Wiley Periodicals, Inc.

Integrated analyses for genetic markers of polycystic ovary syndrome with 9 case-control studies of gene expression profiles.

PubMed

Lu, Chenqi; Liu, Xiaoqin; Wang, Lin; Jiang, Ning; Yu, Jun; Zhao, Xiaobo; Hu, Hairong; Zheng, Saihua; Li, Xuelian; Wang, Guiying

2017-01-10

Due to genetic heterogeneity and variable diagnostic criteria, genetic studies of polycystic ovary syndrome are particularly challenging. Furthermore, lack of sufficiently large cohorts limits the identification of susceptibility genes contributing to polycystic ovary syndrome. Here, we carried out a systematic search of studies deposited in the Gene Expression Omnibus database through August 31, 2016. The present analyses included studies with: 1) patients with polycystic ovary syndrome and normal controls, 2) gene expression profiling of messenger RNA, and 3) sufficient data for our analysis. Ultimately, a total of 9 studies with 13 datasets met the inclusion criteria and were performed for the subsequent integrated analyses. Through comprehensive analyses, there were 13 genetic factors overlapped in all datasets and identified as significant specific genes for polycystic ovary syndrome. After quality control assessment, there were six datasets remained. Further gene ontology enrichment and pathway analyses suggested that differentially expressed genes mainly enriched in oocyte pathways. These findings provide potential molecular markers for diagnosis and prognosis of polycystic ovary syndrome, and need in-depth studies on the exact function and mechanism in polycystic ovary syndrome.

Relationship Between Vitamin D Deficiency and Markers of Metabolic Syndrome Among Overweight and Obese Adults.

PubMed

Kaseb, Fatemeh; Haghighyfard, Kimia; Salami, Maryam-Sadat; Ghadiri-Anari, Akram

2017-06-01

In recent years, metabolic syndrome, obesity, diabetes and cardiovascular disease has had a tremendous elevation growth. Many studies have demonstrated negative correlation between vitamin D deficiency and indexes of metabolic syndrome in obese patients. This study was designed to find the relation between vitamin D deficiency and markers of metabolic syndrome among overweight and obese adults referred to obesity center of Shahid Sadoughi hospital in 2014. Eighty-nine overweight and obese adults (79 women and 10 men), who 13 subjects were overweight and 76 subjects were obese were recruited in this cross-sectional study. Total cholesterol, high-density lipoprotein cholesterol, triglyceride, plasma glucose and vitamin D were measured. IDF criteria were used for identifying subjects with metabolic syndrome. Demographic questionnaire was completed. Statistical analysis was performed using SPSS version 16.0. Fisher exact test, logistic regression, and Spearman correlation coefficient were used. The frequency of vitamin D deficiency was 93.2%. According to IDF criteria, the frequency of metabolic syndrome was 36%. There was no significant relationship between vitamin D deficiency and metabolic syndrome. Among metabolic syndrome indicators, there was a significant direct relationship between vitamin D level with FBS (P=0.013) and SBP (P=0.023). There was no significant relationship between vitamin D deficiency and metabolic syndrome. Due to the lack of relationship between vitamin D deficiency and metabolic syndrome, small number of participants in this study and very low case of normal vitamin D level, further studies are needed.

Bovine placenta: a review on morphology, components, and defects from terminology and clinical perspectives.

PubMed

Peter, Augustine T

2013-10-15

The bovine placenta has been the subject of many studies. Concurrently, several specialized terms have been developed to describe its development, morphology, components, function, and pathology. Many of these terms are simple, some are difficult to understand and use, and others are antiquated and may not be scientifically accurate. Defining and adopting terminology for the bovine placenta that is clear, precise and understandable, and available in a single source is expected to facilitate exchange of clinical and research information. This review presents a brief overview of the current knowledge regarding the bovine placenta and attempts to define terms. In this process, conventional terminology is presented, and contemporary and novel terms are proposed from a biological perspective. For example, use of terms such as syndesmochorial, retained placenta, and large offspring syndrome should be revisited. Furthermore, the clinical relevance of the structure and function of the bovine placenta is reviewed. Finally, terms discussed in this review are summarized (in table format). Copyright © 2013 Elsevier Inc. All rights reserved.

Increased calcium deposits and decreased Ca2+ -ATPase in erythrocytes of ascitic broiler chickens.

PubMed

Li, Kai; Zhao, Lihong; Geng, Guangrui; Ma, Liqin; Dong, Shishan; Xu, Tong; Wang, Jianlin; Wang, Huiyu; Tian, Yong; Qiao, Jian

2011-06-01

The decrease of erythrocyte deformability may be one of the predisposing factors for pulmonary hypertension and ascites in broiler chickens. In mammals, the cytoplasmic calcium is a major regulator of erythrocyte deformability. In this study, the erythrocyte deformability was measured, and the precise locations of Ca2+ and Ca2+ -ATPase in the erythrocytes were investigated in chickens with ascites syndrome induced by low ambient temperature. The results showed that ascitic broilers had higher filtration index of erythrocyte compared with control groups, indicating a decrease in erythrocyte deformability in ascitic broilers. The more calcium deposits were observed in the erythrocytes of ascitic broilers compared with those of the age-matched control birds. The Ca2+ -ATPase reactive grains were significantly decreased on the erythrocyte membranes of ascitic broilers. Our data suggest that accumulation of intracellular calcium and inhibition of Ca2+ -ATPase might be important factors for the reduced deformability of the erythrocytes of ascitic broilers. Copyright © 2010 Elsevier Ltd. All rights reserved.

Computational fluid dynamics and trigeminal sensory examinations of empty nose syndrome patients

PubMed Central

Li, Chengyu; Farag, Alexander A.; Leach, James; Deshpande, Bhakthi; Jacobowitz, Adam; Kim, Kanghyun; Otto, Bradley A.; Zhao, Kai

2017-01-01

Objective The precise pathogenesis of empty nose syndrome (ENS) remains unclear. Various factors such as nasal aerodynamics and sensorineural dysfunction have been suspected, yet, evidence is limited. This study reported the first examination of both nasal aerodynamics and trigeminal sensory factors in actual ENS patients. Study Design Prospective case control. Methods We enrolled 6 patients diagnosed with ENS. Three patients had pre- and post-inferior turbinate (IT) reduction computed tomography (CT) scans, which allowed comparison of their nasal aerodynamics changes through Computational Fluid Dynamic (CFD) simulation. Their symptoms were confirmed through SNOT-22, ENS6Q, acoustic rhinometry and rhinomanometry findings. Nasal trigeminal sensitivity that potentially mediates their perception of airflow, was assessed via menthol lateralization detection thresholds (LDT) and compared with 14 healthy controls. Results Post-surgical reductions in nasal resistance were observed and significantly lower than normal (p<0.05). CFD analysis showed that, paradoxically for all ENS patients, IT reduction did not draw more airflow to the airway surrounding the ITs, but rather resulted in nasal airflow forming into a narrow jet towards the middle meatus region, leaving the airway surrounding the inferior turbinate with significantly reduced airflow intensity and air-mucosal interactions (inferior region flow percentage reduced from 35.7%±15.9% to post-surgery 17.7%±15.7, p<0.05; inferior wall-shear-stress, reduced from 7.5±4.2×10−2 Pa to 3.4±3.1×10−2 Pa, p<0.01). ENS patients also had significantly impaired menthol LDT compared to healthy controls (p<0.005). Conclusion The results indicated that a combinatory of factors, including paradoxically distorted nasal aerodynamic, impaired sensorineural sensitivity, and potential pre-disposing conditions, may contribute to the development of ENS. PMID:28278356

The tool in the brain: apraxia in ADL. Behavioral and neurological correlates of apraxia in daily living.

PubMed

Bieńkiewicz, Marta M N; Brandi, Marie-Luise; Goldenberg, Georg; Hughes, Charmayne M L; Hermsdörfer, Joachim

2014-01-01

Humans differ from other animals in the way they can skilfully and precisely operate or invent tools to facilitate their everyday life. Tools have dominated our home, travel and work environment, becoming an integral step for our motor skills development. What happens when the part of the brain responsible for tool use is damaged in our adult life due to a cerebrovascular accident? How does daily life change when we lose the previously mastered ability to make use of the objects around us? How do patients suffering from compromised tool use cope with food preparation, personal hygiene, grooming, housework, or use of home appliances? In this literature review we present a state of the art for single and multiple tool use research, with a focus on the impact that apraxia (impaired ability to perform tool-based actions) and action disorganization syndrome (ADS; impaired ability to carry out multi-step actions) have on activities of daily living (ADL). Firstly, we summarize the behavioral studies investigating the impact of apraxia and other comorbidity syndromes, such as neglect or visual extinction, on ADL. We discuss the hallmarks of the compromised tool use in terms of the sequencing of action steps, conceptual errors committed, spatial motor control, and temporal organization of the movement. In addition, we present an up-to-date overview of the neuroimaging and lesion analyses studies that provide an insight into neural correlates of tool use in the human brain and functional changes in the neural organization following a stroke, in the context of ADL. Finally we discuss the current practice in neurorehabilitation of ADL in apraxia and ADS aiming at increasing patients' independence.

Ca2+ regulatory mechanisms of exercise protection against coronary artery disease in metabolic syndrome and diabetes.

PubMed

Sturek, Michael

2011-08-01

Chronic exercise attenuates coronary artery disease (CAD) in humans largely independent of reductions in risk factors; thus major protective mechanisms of exercise are directly within the coronary vasculature. Further, tight control of diabetes, e.g., blood glucose, can be detrimental. Accordingly, knowledge of mechanisms by which exercise attenuates diabetic CAD could catalyze development of molecular therapies. Exercise attenuates CAD (atherosclerosis) and restenosis in miniature swine models, which enable precise control of exercise parameters (intensity, duration, and frequency) and characterization of the metabolic syndrome (MetS) and diabetic milieu. Intracellular Ca(2+) is a pivotal second messenger for coronary smooth muscle (CSM) excitation-contraction and excitation-transcription coupling that modulates CSM proliferation, migration, and calcification. CSM of diabetic dyslipidemic Yucatan swine have impaired Ca(2+) extrusion via the plasmalemma Ca(2+) ATPase (PMCA), downregulation of L-type voltage-gated Ca(2+) channels (VGCC), increased Ca(2+) sequestration by the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA), increased nuclear Ca(2+) localization, and greater activation of K channels by Ca(2+) release from the SR. Endurance exercise training prevents Ca(2+) transport changes with virtually no effect on the diabetic milieu (glucose, lipids). In MetS Ossabaw swine transient receptor potential canonical (TRPC) channels are upregulated and exercise training reverses expression and TRPC-mediated Ca(2+) influx with almost no change in the MetS milieu. Overall, exercise effects on Ca(2+) signaling modulate CSM phenotype. Future studies should 1) selectively target key Ca(2+) transporters to determine definitively their causal role in atherosclerosis and 2) combine mechanistic studies with clinical outcomes, e.g., reduction of myocardial infarction.

Functional brain imaging in irritable bowel syndrome with rectal balloon-distention by using fMRI.

PubMed

Yuan, Yao-Zong; Tao, Ran-Jun; Xu, Bin; Sun, Jing; Chen, Ke-Min; Miao, Fei; Zhang, Zhong-Wei; Xu, Jia-Yu

2003-06-01

Irritable bowel syndrome (IBS) is characterized by abdominal pain and changes in stool habits. Visceral hypersensitivity is a key factor in the pathophysiology of IBS. The aim of this study was to examine the effect of rectal balloon-distention stimulus by blood oxygenation level-dependent functional magnetic resonance imaging (BOLD-fMRI) in visceral pain center and to compare the distribution, extent, and intensity of activated areas between IBS patients and normal controls. Twenty-six patients with IBS and eleven normal controls were tested for rectal sensation, and the subjective pain intensity at 90 ml and 120 ml rectal balloon-distention was reported by using Visual Analogue Scale. Then, BOLD-fMRI was performed at 30 ml, 60 ml, 90 ml, and 120 ml rectal balloon-distention in all subjects. Rectal distention stimulation increased the activity of anterior cingulate cortex (35/37), insular cortex (37/37), prefrontal cortex (37/37), and thalamus (35/37) in most cases. At 120 ml of rectal balloon-distention, the activation area and percentage change in MR signal intensity of the regions of interest (ROI) at IC, PFC, and THAL were significantly greater in patients with IBS than that in controls. Score of pain sensation at 90 ml and 120 ml rectal balloon-distention was significantly higher in patients with IBS than that in controls. Using fMRI, some patients with IBS can be detected having visceral hypersensitivity in response to painful rectal balloon-distention. fMRI is an objective brain imaging technique to measure the change in regional cerebral activation more precisely. In this study, IC and PFC of the IBS patients were the major loci of the CNS processing of visceral perception.

Lorcaserin in Obese and Overweight Patients Taking Prohibited Serotonergic Agents: A Retrospective Analysis.

PubMed

Nguyen, Charles T; Zhou, Sharon; Shanahan, William; Fain, Randi

2016-06-01

Lorcaserin is a selective serotonin 2C receptor (5-HT2C) agonist approved in the United States for use in chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. Its pharmacologic activity is limited to 5-HT subtype 2 receptors. The potency of lorcaserin for the 5-HT2C receptor is 14-fold greater than its potency for the 5-HT2A receptor and 61-fold greater than its potency for the 5-HT2B receptor. Although 5-HT receptors have been implicated in serotonin syndrome, the precise pathogenesis is unknown. Given a theoretic risk for this syndrome in patients administered lorcaserin either alone or in combination with certain serotonergic agents (eg, selective serotonin reuptake inhibitors [SSRIs] and serotonin-norepinephrine reuptake inhibitors [SNRIs]), patients taking prohibited serotonergic agents were excluded from the Phase III clinical trials. This retrospective analysis evaluated the tolerability of lorcaserin in patients who took protocol-allowed or proscribed serotonergic agents for varying durations of up to 1 year during the BLOOM, BLOSSOM, and BLOOM-DM studies. Patients randomly assigned to receive either lorcaserin 10 mg QD, lorcaserin 10 mg BID, or placebo and who took a spectrum of serotonergic agents were evaluated at week 52 of treatment (814 and 624 patients receiving lorcaserin and placebo, respectively, were found to have taken allowed or prohibited serotonergic agents during these trials). After the use of a proscribed serotonergic agent was discovered, these patients were discontinued from the trial and followed. None of the patients in the serotonergic agent subpopulation or in the overall safety population met the clinical criteria of serotonin syndrome. The proportions of patients experiencing any adverse event (AE) were balanced in the lorcaserin and placebo groups in the prohibited serotonergic agent subpopulation. The prevalences of the most common AEs were similar between the serotonergic agent subpopulation and the overall safety population. The concurrent use of lorcaserin and prohibited or allowed serotonergic agents did not appear to have increased the spectrum or intensity of AEs potentially associated with serotonin excess in this limited dataset. However, the sample population was too small to rule out an effect on a rare event such as serotonin syndrome. ClinicalTrials.gov identifiers: NCT00395135, NCT00603902, and NCT00603291. Published by Elsevier Inc.

The Capgras syndrome in paranoid schizophrenia.

PubMed

Silva, J A; Leong, G B

1992-01-01

Capgras syndrome is characterized by a delusion of impostors who are thought to be physically similar but psychologically distinct from the misidentified person. This syndrome is generally thought to be relatively rare. Most of our knowledge about Capgras syndrome derives from single case studies and small series of cases usually from diagnostically heterogeneous groups. In this article, a series of 31 patients suffering from both paranoid schizophrenia and Capgras syndrome is described. Issues pertaining to the phenomenology of Capgras syndrome, the possible relation between Capgras syndrome and other delusional misidentification syndromes, and a neurobiological hypothesis aimed at explaining Capgras syndrome are discussed.

Relationship between chronic nonurological associated somatic syndromes and symptom severity in urological chronic pelvic pain syndromes: baseline evaluation of the MAPP study.

PubMed

Krieger, John N; Stephens, Alisa J; Landis, J Richard; Clemens, J Quentin; Kreder, Karl; Lai, H Henry; Afari, Niloofar; Rodríguez, Larissa; Schaeffer, Anthony; Mackey, Sean; Andriole, Gerald L; Williams, David A

2015-04-01

We used MAPP data to identify participants with urological chronic pelvic pain syndromes only or a chronic functional nonurological associated somatic syndrome in addition to urological chronic pelvic pain syndromes. We characterized these 2 subgroups and explored them using 3 criteria, including 1) MAPP eligibility criteria, 2) self-reported medical history or 3) RICE criteria. Self-reported cross-sectional data were collected on men and women with urological chronic pelvic pain syndromes, including predominant symptoms, symptom duration and severity, nonurological associated somatic syndrome symptoms and psychosocial factors. Of 424 participants with urological chronic pelvic pain syndromes 162 (38%) had a nonurological associated somatic syndrome, including irritable bowel syndrome in 93 (22%), fibromyalgia in 15 (4%), chronic fatigue syndrome in 13 (3%) and multiple syndromes in 41 (10%). Of 233 females 103 (44%) had a nonurological associated somatic syndrome compared to 59 of 191 males (31%) (p = 0.006). Participants with a nonurological associated somatic syndrome had more severe urological symptoms and more frequent depression and anxiety. Of 424 participants 228 (54%) met RICE criteria. Of 228 RICE positive participants 108 (47%) had a nonurological associated somatic syndrome compared to 54 of 203 RICE negative patients (28%) with a nonurological associated somatic syndrome (p < 0.001). Nonurological associated somatic syndromes represent important clinical characteristics of urological chronic pelvic pain syndromes. Participants with a nonurological associated somatic syndrome have more severe symptoms, longer duration and higher rates of depression and anxiety. RICE positive patients are more likely to have a nonurological associated somatic syndrome and more severe symptoms. Because nonurological associated somatic syndromes are more common in women, future studies must account for this potential confounding factor in urological chronic pelvic pain syndromes. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

An Exploration of the Use of Eye Gaze and Gestures in Females with Rett Syndrome

ERIC Educational Resources Information Center

Urbanowicz, Anna; Downs, Jenny; Girdler, Sonya; Ciccone, Natalie; Leonard, Helen

2016-01-01

Purpose: This study investigated the communicative use of eye gaze and gestures in females with Rett syndrome. Method: Data on 151 females with Rett syndrome participating in the Australian Rett Syndrome Database was used in this study. Items from the Communication and Symbolic Behavior Scales Developmental Profile Infant-Toddler Checklist…

Prevalence of metabolic syndrome in Chinese psoriasis patients: A hospital-based cross-sectional study.

PubMed

Gui, Xin-Yu; Yu, Xiao-Ling; Jin, Hong-Zhong; Zuo, Ya-Gang; Wu, Chao

2018-01-01

Psoriasis, a chronic autoimmune skin disorder, is believed to contribute to cardiovascular diseases and metabolic syndrome. Psoriasis's association with the components of metabolic syndrome has been reported previously. However, large-scale cross-sectional studies about psoriasis and metabolic syndrome are rare in China. We assessed the prevalence of metabolic syndrome in Chinese psoriasis patients and controls. A total of 859 psoriasis patients and 1,718 controls were recruited in an age- and sex-matched cross-sectional study. Metabolic syndrome occurred in 14.3% of the psoriasis patients as opposed to 10.0% of the control participants (P = 0.001). Psoriasis patients had a higher prevalence of overweight/obesity, hyperglycemia and dyslipidemia when compared with controls. Meanwhile, psoriasis patients with metabolic syndrome were older, and had an older age of onset and a longer disease duration when compared with those without metabolic syndrome. The prevalence of metabolic syndrome is higher in the Chinese psoriatic population, which can favor cardiovascular events. The present study strengthens the value of treating psoriasis patients not only dealing with the skin lesions, and we suggest appropriate screening and relevant health education be carried out in the treatment of psoriasis patients. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.

Dietary Magnesium Intake and Metabolic Syndrome in the Adult Population: Dose-Response Meta-Analysis and Meta-Regression

PubMed Central

Ju, Sang-Yhun; Choi, Whan-Seok; Ock, Sun-Myeong; Kim, Chul-Min; Kim, Do-Hoon

2014-01-01

Increasing evidence has suggested an association between dietary magnesium intake and metabolic syndrome. However, previous research examining dietary magnesium intake and metabolic syndrome has produced mixed results. Our objective was to determine the relationship between dietary magnesium intake and metabolic syndrome in the adult population using a dose-response meta-analysis. We searched the PubMed, Embase and the Cochrane Library databases from August, 1965, to May, 2014. Observational studies reporting risk ratios with 95% confidence intervals (CIs) for metabolic syndrome in ≥3 categories of dietary magnesium intake levels were selected. The data extraction was performed independently by two authors, and the quality of the studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). Based on eight cross-sectional studies and two prospective cohort studies, the pooled relative risks of metabolic syndrome per 150 mg/day increment in magnesium intake was 0.88 (95% CI, 0.84–0.93; I2 = 36.3%). The meta-regression model showed a generally linear, inverse relationship between magnesium intake (mg/day) and metabolic syndrome. This dose-response meta-analysis indicates that dietary magnesium intake is significantly and inversely associated with the risk of metabolic syndrome. However, randomized clinical trials will be necessary to address the issue of causality and to determine whether magnesium supplementation is effective for the prevention of metabolic syndrome. PMID:25533010

Connected Gene Communities Underlie Transcriptional Changes in Cornelia de Lange Syndrome.

PubMed

Boudaoud, Imène; Fournier, Éric; Baguette, Audrey; Vallée, Maxime; Lamaze, Fabien C; Droit, Arnaud; Bilodeau, Steve

2017-09-01

Cornelia de Lange syndrome (CdLS) is a complex multisystem developmental disorder caused by mutations in cohesin subunits and regulators. While its precise molecular mechanisms are not well defined, they point toward a global deregulation of the transcriptional gene expression program. Cohesin is associated with the boundaries of chromosome domains and with enhancer and promoter regions connecting the three-dimensional genome organization with transcriptional regulation. Here, we show that connected gene communities, structures emerging from the interactions of noncoding regulatory elements and genes in the three-dimensional chromosomal space, provide a molecular explanation for the pathoetiology of CdLS associated with mutations in the cohesin-loading factor NIPBL and the cohesin subunit SMC1A NIPBL and cohesin are important constituents of connected gene communities that are centrally positioned at noncoding regulatory elements. Accordingly, genes deregulated in CdLS are positioned within reach of NIPBL- and cohesin-occupied regions through promoter-promoter interactions. Our findings suggest a dynamic model where NIPBL loads cohesin to connect genes in communities, offering an explanation for the gene expression deregulation in the CdLS. Copyright © 2017 by the Genetics Society of America.

Respiratory mechanics to understand ARDS and guide mechanical ventilation.

PubMed

Mauri, Tommaso; Lazzeri, Marta; Bellani, Giacomo; Zanella, Alberto; Grasselli, Giacomo

2017-11-30

As precision medicine is becoming a standard of care in selecting tailored rather than average treatments, physiological measurements might represent the first step in applying personalized therapy in the intensive care unit (ICU). A systematic assessment of respiratory mechanics in patients with the acute respiratory distress syndrome (ARDS) could represent a step in this direction, for two main reasons. Approach and Main results: On the one hand, respiratory mechanics are a powerful physiological method to understand the severity of this syndrome in each single patient. Decreased respiratory system compliance, for example, is associated with low end expiratory lung volume and more severe lung injury. On the other hand, respiratory mechanics might guide protective mechanical ventilation settings. Improved gravitationally dependent regional lung compliance could support the selection of positive end-expiratory pressure and maximize alveolar recruitment. Moreover, the association between driving airway pressure and mortality in ARDS patients potentially underlines the importance of sizing tidal volume on respiratory system compliance rather than on predicted body weight. The present review article aims to describe the main alterations of respiratory mechanics in ARDS as a potent bedside tool to understand severity and guide mechanical ventilation settings, thus representing a readily available clinical resource for ICU physicians.

Refractory chronic cough, or the need to focus on the relationship between the larynx and the esophagus

PubMed Central

2013-01-01

In this review we question the current way of handling tackle a problem of chronic cough, especially by the excessive number of patients who can not find complete relief from your cough by anatomical diagnosis of universal use. From the field of Otolaryngology new perspectives arise now considering the larynx as a preferential afferent stimuli cough reflex arc. Also the constitution laryngopharyngeal reflux gas and new approaches to non-acid reflux and the local action of pepsin in laryngeal deserving of a joint review, which can illuminate new ways to handle the problem of chronic refractory cough. We believe that the chronic cough syndrome hpersensitivity as more precise label for chronic cough, should place particular emphasis on laryngeal sensory neuropathy as cough and reflux the influence that may have on their maintenance, and thereby causes definitely wide related to the syndrome if the larynx is incorporated, place greater number of afferent nerves of chronic cough, which are sure to cover much of the case of refractory cough remain without a satisfactory solution. The close collaboration between Otolaryngology, Gastroenterology and Pneumology in a patient with refractory chronic cough seems now an unavoidable necessity. PMID:23552099

Mold allergy: is it real and what do we do about it?

PubMed

Rudert, Amanda; Portnoy, Jay

2017-08-01

fungi produce substances that contain pathogen-associated molecular patterns (pamps) and damage-associated molecular patterns (damps) which bind to pattern recognition receptors, stimulating innate immune responses in humans. they also produce allergens that induce production of specific ige. Areas covered: In this review we cover both innate and adaptive immune responses to fungi. Some fungal products can activate both innate and adaptive responses and in doing so, cause an intense and complex health effects. Methods of testing for fungal allergy and evidence for clinical treatment including environmental control are also discussed. In addition, we describe controversial issues including the role of Stachybotrys and mycotoxins in adverse health effects. Expert commentary: Concerns about long-term exposure to fungi have led some patients, attorneys and fungus advocates to promote fears about a condition that has been termed toxic mold syndrome. This syndrome is associated with vague symptoms and is believed to be due to exposure to mycotoxins, though this connection has not been proven. Ultimately, more precise methods are needed to measure both fungal exposure and the resulting health effects. Once that such methods become available, much of the speculation will be replaced by knowledge.

DNA mismatch repair protein deficient non-neoplastic colonic crypts: a novel indicator of Lynch syndrome.

PubMed

Pai, Rish K; Dudley, Beth; Karloski, Eve; Brand, Randall E; O'Callaghan, Neil; Rosty, Christophe; Buchanan, Daniel D; Jenkins, Mark A; Thibodeau, Stephen N; French, Amy J; Lindor, Noralane M; Pai, Reetesh K

2018-06-08

Lynch syndrome is the most common form of hereditary colorectal carcinoma. However, establishing the diagnosis of Lynch syndrome is challenging, and ancillary studies that distinguish between sporadic DNA mismatch repair (MMR) protein deficiency and Lynch syndrome are needed, particularly when germline mutation studies are inconclusive. The aim of this study was to determine if MMR protein-deficient non-neoplastic intestinal crypts can help distinguish between patients with and without Lynch syndrome. We evaluated the expression of MMR proteins in non-neoplastic intestinal mucosa obtained from colorectal surgical resection specimens from patients with Lynch syndrome-associated colorectal carcinoma (n = 52) and patients with colorectal carcinoma without evidence of Lynch syndrome (n = 70), including sporadic MMR protein-deficient colorectal carcinoma (n = 30), MMR protein proficient colorectal carcinoma (n = 30), and "Lynch-like" syndrome (n = 10). MMR protein-deficient non-neoplastic colonic crypts were identified in 19 of 122 (16%) patients. MMR protein-deficient colonic crypts were identified in 18 of 52 (35%) patients with Lynch syndrome compared to only 1 of 70 (1%) patients without Lynch syndrome (p < 0.001). This one patient had "Lynch-like" syndrome and harbored two MSH2-deficient non-neoplastic colonic crypts. MMR protein-deficient non-neoplastic colonic crypts were not identified in patients with sporadic MMR protein-deficient or MMR protein proficient colorectal carcinoma. Our findings suggest that MMR protein-deficient colonic crypts are a novel indicator of Lynch syndrome, and evaluation for MMR protein-deficient crypts may be a helpful addition to Lynch syndrome diagnostics.

Objective studies of the face of Noonan, Cardio-facio-cutaneous, and Costello syndromes: A comparison of three disorders of the Ras/MAPK signaling pathway.

PubMed

Allanson, Judith E

2016-10-01

Noonan, Cardio-facio-cutaneous, and Costello syndromes are disorders of the Ras/MAPK pathway that share many clinical features. This observational and anthropometric study was conducted to describe the key facial features of each syndrome in order to improve discrimination between the three conditions, particularly in young children where diagnosis is most challenging. Direct measurement of the head and face was used to enhance diagnostic accuracy, and identify the most unusual or specific dimensions. The Noonan syndrome cohort included 123 individuals, aged 6 months to 41 years. There were 20 children and adolescents with Cardio-facio-cutaneous syndrome, and 28 individuals with Costello syndrome, aged 1-32 years. The facial phenotypes of these syndromes, particularly Noonan syndrome, are well-described but objective data have not been published in peer-reviewed literature. In this study, subjective observations, in the main, were validated by anthropometry with one exception. In individuals with Costello syndrome, mouth width was normal, thus the impression of wide mouth is likely due to full lips or the mouth being viewed in relation to a narrow lower face. When the three conditions were compared objectively, syndrome-specific pattern profiles showed high concordance in early life. At older ages, Cardio-facio-cutaneous syndrome was distinguished by increased width of the mid/lower face, and reduced growth of maxillary and mandibular dimensions was noted in both Noonan and Costello syndromes. Despite substantial similarities in face shape in older individuals with these two conditions, bulbous nasal tip, full lips, and an apparently wide mouth in those with Costello Syndrome facilitate discrimination from Noonan syndrome. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Neuroligins Provide Molecular Links Between Syndromic and Non-Syndromic Autism

PubMed Central

Singh, Sandeep K.; Eroglu, Cagla

2014-01-01

Autism is a common and heritable neuropsychiatric disorder that can be categorized into two types: syndromic and non-syndromic, the former of which are associated with other neurological disorders or syndromes. Molecular and functional links between syndromic and non-syndromic autism genes were lacking until studies aimed at understanding role of trans-synaptic adhesion molecule neuroligin, which is associated with non-syndromic autism, provided important connections. Here, we integrate data from these studies into a model of how neuroligin functions to control synaptic connectivity in the central nervous system and how neuroligin dysfunction may participate in the pathophysiology of autism. Understanding the complex functional interactions between neuroligins and other autism-associated proteins at the synapse is crucial to understand the pathology of autism. This understanding might bring us closer to development of therapeutic approaches for autism. PMID:23838185

Addressing challenging behaviour in children with Down syndrome: the use of applied behaviour analysis for assessment and intervention.

PubMed

Feeley, Kathleen M; Jones, Emily A

2006-09-01

Children with Down syndrome are at an increased risk for engaging in challenging behaviour that may be part of a behavioural phenotype characteristic of Down syndrome. The methodology of applied behaviour analysis has been demonstrated effective with a wide range of challenging behaviours, across various disabilities. Applications to children with Down syndrome and the examination of behaviourally based strategies to specifically address the unique characteristics of children with Down syndrome are limited. However, there are several studies in which a subset of the participants did have Down syndrome. A handful of these studies are reviewed within the context of functional behaviour assessment and Positive Behavioural Supports. Drawing from these studies and the behavioural literature, as well as the authors' clinical experience and research, suggestions regarding early intervention for challenging behaviour with children with Down syndrome are provided.

Incidence of Radiologically Isolated Syndrome: A Population-Based Study.

PubMed

Forslin, Y; Granberg, T; Jumah, A Antwan; Shams, S; Aspelin, P; Kristoffersen-Wiberg, M; Martola, J; Fredrikson, S

2016-06-01

Incidental MR imaging findings resembling MS in asymptomatic individuals, fulfilling the Okuda criteria, are termed "radiologically isolated syndrome." Those with radiologically isolated syndrome are at high risk of their condition converting to MS. The epidemiology of radiologically isolated syndrome remains largely unknown, and there are no population-based studies, to our knowledge. Our aim was to study the population-based incidence of radiologically isolated syndrome in a high-incidence region for MS and to evaluate the effect on radiologically isolated syndrome incidence when revising the original radiologically isolated syndrome criteria by using the latest radiologic classification for dissemination in space. All 2272 brain MR imaging scans in 1907 persons obtained during 2013 in the Swedish county of Västmanland, with a population of 259,000 inhabitants, were blindly evaluated by a senior radiologist and a senior neuroradiologist. The Okuda criteria for radiologically isolated syndrome were applied by using both the Barkhof and Swanton classifications for dissemination in space. Assessments of clinical data were performed by a radiology resident and a senior neurologist. The cumulative incidence of radiologically isolated syndrome was 2 patients (0.1%), equaling an incidence rate of 0.8 cases per 100,000 person-years, in a region with an incidence rate of MS of 10.2 cases per 100,000 person-years. There was no difference in the radiologically isolated syndrome incidence rate when applying a modified version of the Okuda criteria by using the newer Swanton classification for dissemination in space. Radiologically isolated syndrome is uncommon in a high-incidence region for MS. Adapting the Okuda criteria to use the dissemination in space-Swanton classification may be feasible. Future studies on radiologically isolated syndrome may benefit from a collaborative approach to ensure adequate numbers of participants. © 2016 by American Journal of Neuroradiology.

Clinicopathologic, Immunohistochemical, and Molecular Features of Histiocytoid Sweet Syndrome.

PubMed

Alegría-Landa, Victoria; Rodríguez-Pinilla, Socorro María; Santos-Briz, Angel; Rodríguez-Peralto, José Luis; Alegre, Victor; Cerroni, Lorenzo; Kutzner, Heinz; Requena, Luis

2017-07-01

Histiocytoid Sweet syndrome is a rare histopathologic variant of Sweet syndrome. The nature of the histiocytoid infiltrate has generated considerable controversy in the literature. The main goal of this study was to conduct a comprehensive overview of the immunohistochemical phenotype of the infiltrate in histiocytoid Sweet syndrome. We also analyze whether this variant of Sweet syndrome is more frequently associated with hematologic malignancies than classic Sweet syndrome. This is a retrospective case series study of the clinicopathologic, immunohistochemical, and molecular features of 33 patients with a clinicopathologic diagnosis of histiocytoid Sweet syndrome was conducted in the dermatology departments of 5 university hospitals and a private laboratory of dermatopathology. The clinical, histopathological, immunohistochemical, and follow-up features of 33 patients with histiocytoid Sweet syndrome were analyzed. In some cases, cytogenetic studies of the dermal infiltrate were also performed. We compare our findings with those of the literature. The dermal infiltrate from the 33 study patients (20 female; median age, 49 years; age range, 5-93 years; and 13 male; median age, 42 years; age range, 4-76 years) was mainly composed of myeloperoxidase-positive immature myelomonocytic cells with histiocytoid morphology. No cytogenetic anomalies were found in the infiltrate except in 1 case in which neoplastic cells of chronic myelogenous leukemia were intermingled with the cells of histiocytoid Sweet syndrome. Authentic histiocytes were also found in most cases, with a mature immunoprofile, but they appeared to be a minor component of the infiltrate. Histiocytoid Sweet syndrome was not more frequently related with hematologic malignancies than classic neutrophilic Sweet syndrome. The dermal infiltrate of cutaneous lesions of histiocytoid Sweet syndrome is composed mostly of immature cells of myeloid lineage. This infiltrate should not be interpreted as leukemia cutis.

Magnitude and management of metabolic syndrome in Spain in 2008-2010: the ENRICA study.

PubMed

Guallar-Castillón, Pilar; Pérez, Raúl Francisco; López García, Esther; León-Muñoz, Luz M; Aguilera, M Teresa; Graciani, Auxiliadora; Gutiérrez-Fisac, Juan Luis; Banegas, José R; Rodríguez-Artalejo, Fernando

2014-05-01

Few studies in Spain have reported the distribution of metabolic syndrome using the harmonized definition and that of premorbid metabolic syndrome, which consists of metabolic syndrome without diabetes mellitus or cardiovascular disease. Moreover, their regional distributions and clinical management are unknown. The present study examined the distributions and clinical management of both syndromes in Spain. This cross-sectional study was performed from 2008 to 2010 in 11 149 representative individuals of the Spanish population aged 18 years or older. Data were obtained through standardized physical examination, and analytical measurements were done in a central laboratory. The prevalences (95% confidence interval) of metabolic syndrome and premorbid metabolic syndrome were 22.7% (21.7%-23.7%) and 16.9% (16.0%-17.8%), respectively. The frequency of both syndromes increased with age and was higher in men than in women up to 65 years; above this age, the frequency was higher in women. The communities of the south of Spain and the Balearic and Canary islands had the highest prevalence of both syndromes, in some regions reaching double that of the community with the lowest prevalence. About one third of patients with premorbid metabolic syndrome reported that they had not received health recommendations to improve their lifestyles; of those that did receive advice, adherence was low, particularly for reducing weight (31.9%) and salt intake (38.3%). The prevalence of metabolic syndrome is high in Spain and considerable geographical differences exist in its distribution. There is substantial room for improvement in the clinical management of premorbid metabolic syndrome. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

Primary Ovarian Insufficiency (POI)

MedlinePlus

... Research Information Find a Study Resources and Publications Turner Syndrome Condition Information NICHD Research Information Find a Study ... site for more information. Most women who have Turner syndrome develop POI. Turner syndrome is a condition in ...

Headache in Behçet's syndrome: review of literature and NYU Behçet's syndrome center experience.

PubMed

Vishwanath, Vijay; Wong, Ericka; Crystal, Sara C; Robbins, Matthew S; Filopoulos, Maria; Lipton, Richard B; Yazici, Yusuf; Kister, Ilya

2014-09-01

Headache, a common and disabling symptom in Behçet's syndrome, may be associated with a variety of neurologic syndromes and ocular inflammation, or may present as an isolated feature. Our objective is to describe the various neurologic and ocular syndromes of Behçet's syndrome of which headache is a symptom, and to review the features of isolated headaches in Behçet's. We also report results of a study of headache in Behçet's syndrome patients who are followed at NYU Hospital for Joint Diseases, the first study of its kind in North American patients, and the first to document prevalence of both episodic and chronic daily headache in Behçet's.

Comparing the Broad Socio-Cognitive Profile of Youth with Williams Syndrome and 22Q11.2 Deletion Syndrome

ERIC Educational Resources Information Center

Weisman, O.; Feldman, R.; Burg-Malki, M.; Keren, M.; Geva, R.; Diesendruck, G.; Gothelf, D.

2017-01-01

Background: Numerous studies have assessed the socio-cognitive profile in Williams syndrome (WS) and, independently, in 22q11.2 deletion syndrome (22q11.2DS). Yet, a cross-syndrome comparison of these abilities between individuals with these two syndromes with known social deficits has not been conducted. Methods: Eighty-two children participated…

A Cross-Syndrome Study of the Development of Holistic Face Recognition in Children with Autism, Down Syndrome, and Williams Syndrome

ERIC Educational Resources Information Center

Annaz, Dagmara; Karmiloff-Smith, Annette; Johnson, Mark H.; Thomas, Michael S. C.

2009-01-01

We report a cross-syndrome comparison of the development of holistic processing in face recognition in school-aged children with developmental disorders: autism, Down syndrome, and Williams syndrome. The autism group was split into two groups: one with high-functioning children and one with low-functioning children. The latter group has rarely…

Association of Serum Uric Acid With Cardiometabolic Risk Factors and Metabolic Syndrome in Iranian Adolescents: the CASPIAN-III Study.

PubMed

Safiri, Saeid; Qorbani, Mostafa; Heshmat, Ramin; Tajbakhsh, Ramin; Eslami Shahr Babaki, Amir; Djalalinia, Shirin; Motlagh, Mohammad Esmaeil; Tajadini, Mohammad Hasan; Asayesh, Hamid; Safari, Omid; Kelishadi, Roya

2016-05-01

There is controversial evidence on association of serum acid uric (SUA) with cardiometabolic risk factors and metabolic syndrome in adults. This study aimed to investigate the associations of SUA levels, components of metabolic syndrome, and other cardiometabolic risk factors, in a nationally representative sample of Iranian adolescents. This study included 132 participants who met the criteria of metabolic syndrome and 235 participants without metabolic syndrome. The participants were grouped according to the tertiles of SUA. Metabolic syndrome was defined according to the Adult Treatment Panel III criteria modified for children and adolescents. The relationship between SUA and cardiometabolic risk factors and metabolic syndrome was assessed by multivariable logistic regression analysis. The mean age of the participants was 15.21 ± 2.35 years, with no significant difference between the boys and the girls. The participants whose SUA was categorized in the 2nd tertile and those falling into the 3rd tertile had significantly higher systolic blood pressure (P < .001) as compared with the lower tertile(s). A similar trend was documented for the overall high blood pressure. Metabolic syndrome was associated with the 2nd and 3rd tertiles of SUA as compared to the lower tertile(s), in the adjusted model (P < .001), with the risk increasing by at least 2 times. Our study showed that those adolescents with metabolic syndrome had higher SUA levels. Its association with some components of metabolic syndrome supports that SUA might be an additional component of metabolic syndrome even during adolescence.

Prevalence of metabolic syndrome in Middle-East countries: Meta-analysis of cross-sectional studies.

PubMed

Ansarimoghaddam, Alireza; Adineh, Hosein Ali; Zareban, Iraj; Iranpour, Sohrab; HosseinZadeh, Ali; Kh, Framanfarma

Metabolic syndrome is an important metabolic disorder which impose noticeable burden on health system. We aimed to review and imply the prevalence of it in Middle-East countries. present study was a systematic review to present overview about metabolic disorder in Middle East. Electronic literature search of Medline database and Google scholar were done for English-language articles without time filtering, as well as for population-based or national studies of the prevalence of metabolic syndrome. The fallowing search terms were used simultaneously: prevalence of " metabolic syndrome" and "national study", "prevalence of metabolic syndrome in Middle East", "prevalence of metabolic syndrome" and "name of country", "metabolic syndrome &name of country". Additionally, relevant articles in bibliography were searched. Analysis of data was carried out in STATA version 11.0. out of 456 studies in first-step searching (selecting by title) 59 studies were recruited and reviewed. Prevalence of metabolic syndrome fluctuated by country and time of study. This amount was 2.2-44% in Turkish, 16-41% in Saudi-Arabia, 14-63 in Pakistan, 26-33 in Qatar, 9-36 in Kuwait, 22-50 in Emirate, 6-42 in Iran, and up to 23 in Yemen. Pooled estimate was 25%. Attributable risk for cardiovascular disease, coronary heart disease, and stroke was 15.87, 11.7, and 16.23, respectively. The prevalence rate of metabolic syndrome is high and it is noticeable cause for stroke, coronary heart disease, and cardiovascular disease. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Prevalence of Semicircular Canal Hypoplasia in Patients With CHARGE Syndrome: 3C Syndrome.

PubMed

Wineland, Andre; Menezes, Maithilee D; Shimony, Joshua S; Shinawi, Marwan S; Hullar, Timothy E; Hirose, Keiko

2017-02-01

CHARGE syndrome refers to a syndrome involving coloboma, heart defects, atresia choanae, retardation of growth and development, genitourinary disorders, and ear anomalies. However, Verloes revised the characteristics of CHARGE syndrome in 2005 to define this syndrome more broadly. Deficiency of the semicircular canals is now a major criterion for CHARGE syndrome. To characterize patients with CHARGE syndrome at our center using Verloes' criteria and to reevaluate the nomenclature for this condition. We performed a medical chart review of patients with CHARGE syndrome and reviewed their temporal bone imaging studies at a tertiary care children's hospital affiliated with Washington University in St Louis. Two authors independently reviewed each imaging study (A.W. and K.H.). Radiologic studies, physical findings, genetic tests, and other diagnostic tests were included. Patients with no temporal bone imaging studies were excluded. Eighteen children were included in this study; 13 children (72%) were male, and the mean (median; range) age of patients at the time of inner ear imaging studies was 2 years (4.5 years; 8 months to 8 years). Coloboma was present in 13 patients (72%) and choanal atresia in 5 (28%); semicircular canal anomalies were present in all patients. Additionally, 13 patients (72%) were diagnosed as having hindbrain anomalies, 17 (94%) as having endocrine disorders, 17 (94%) as having mediastinal organ malformations, and all as having middle or external ear abnormalities and development delay. Cleft lip and cleft palate were found in 6 of 14 patients (43%) who did not have choanal atresia. We tested 16 patients for mutations in the CHD7 gene; 10 were positive (63%) for mutations, 4 (25%) were negative, and 2 (13%) were inconclusive. Semicircular canal anomalies were the most consistent finding in our patients with CHARGE syndrome. Given the high prevalence of semicircular canal hypoplasia and importance of imaging for diagnosing CHARGE syndrome, we propose changing the term CHARGE syndrome to 3C syndrome to emphasize the importance of the semicircular canals and to recall the 3 major criteria for diagnosis: coloboma, choanal atresia, and semicircular canal anomaly. The nomenclature would also reference the 3 semicircular canals in each ear. This new name for CHARGE syndrome would provide a mnemonic and focus the disease on the most important clinical criteria for diagnosis.

Assessment of metabolic syndrome in Kashmiri population with type 2 diabetes employing the standard criteria's given by WHO, NCEPATP III and IDF.

PubMed

Lone, Shafat; Lone, Kouser; Khan, Saika; Pampori, Rafiq Ahmed

2017-12-01

Around 20-25 percent of the world's adult populations have the metabolic syndrome and they are twice as likely to die from heart attack or stroke compared with people without the syndrome. The World Health Organization proposed a definition for the metabolic syndrome in 1998 and later on NCEP ATPIII and IDF provided new definitions of this syndrome in 2001 and 2003 respectively. Very few studies have compared the different definitions to diagnose the metabolic syndrome in type two diabetics in India while as for Kashmir valley no such documented study has been carried out till date. To study the prevalence of metabolic syndrome in type 2 Kashmir diabetics and to find out the degree of agreement between three different criteria given by WHO, NCEPATPIII and IDF for diagnosis of metabolic syndrome. A cross sectional study was conducted in one of the two tertiary care hospitals of Kashmir, India. About 1000 patients were selected and their demographic, clinical and biochemical parameters were studied after obtaining informed consent from each patient. Prevalance of metabolic syndrome was found to be highest(84.5%) while using WHO definition.Kappa statistic between WHO, ATP III and WHO, IDF definitions was 0.697 (95% CI 0.637-0.754) and 0.775 (95%CI 0.72-0.82) respectively while the degree of agreement between IDF and ATP III definitions was highest with kappa of 0.851 (95%CI 0.810-0.889). Our study warrants for interventions to prevent the progression towards this syndrome among type 2 diabetics as early as the diagnosis of diabetes is made. Copyright © 2017 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Relationship between metabolic syndrome and its components with bone densitometry in postmenopausal women.

PubMed

Abbasi, Mahnaz; Farzam, Seyed Amir; Mamaghani, Zahra; Yazdi, Zohreh

2017-11-01

Prevention of osteoporosis and bone fracture and the relationship between metabolic syndrome and bone density are controversial issues. The aim of this study was to evaluate the association between metabolic syndrome and its components with bone mineral density in post menopausal women referred for bone mineral density (BMD) test. A total of 143 postmenopausal women with at least one year of menopause experience participated in this cross-sectional study. Demographic and anthropometric characteristics for all participants were collected. Also, biochemical parameters including fasting blood sugar, Cholesterol (HDL and LDL), triglyceride were measured. Association between the components of metabolic syndrome and bone densitometry were analyzed by statistical methods. In this study, 72% of participants did not have metabolic syndrome. Among them, 43.4% and 28.7% had osteoporosis and normal density, respectively. Of remaining participants with metabolic syndrome, 12.6% and 15.4% had osteoporosis and normal density, respectively. Among the metabolic syndrome components, waist circumference, HDL cholesterol, and waist to hip ratio were significantly associated with bone mass (P<0.05). Osteoporotic women had lower waist circumference and waist to hip ratio and higher HDL than women without osteoporosis. On the other hand, women with metabolic syndrome did not have significant differences than women without metabolic syndrome in terms of lumbar and femoral neck density (P>0.05). Results from this study showed that metabolic syndrome and its components did not induce bone mass loss. The discrepancies of the studies in this area call for more large scale studies in population so as to prevent women problems in this area. Copyright © 2016 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Association of Sedentary Behaviour with Metabolic Syndrome: A Meta-Analysis

PubMed Central

Edwardson, Charlotte L.; Gorely, Trish; Davies, Melanie J.; Gray, Laura J.; Khunti, Kamlesh; Wilmot, Emma G.; Yates, Thomas; Biddle, Stuart J. H.

2012-01-01

Background In recent years there has been a growing interest in the relationship between sedentary behaviour (sitting) and health outcomes. Only recently have there been studies assessing the association between time spent in sedentary behaviour and the metabolic syndrome. The aim of this study is to quantify the association between sedentary behaviour and the metabolic syndrome in adults using meta-analysis. Methodology/Principal Findings Medline, Embase and the Cochrane Library were searched using medical subject headings and key words related to sedentary behaviours and the metabolic syndrome. Reference lists of relevant articles and personal databases were hand searched. Inclusion criteria were: (1) cross sectional or prospective design; (2) include adults ≥18 years of age; (3) self-reported or objectively measured sedentary time; and (4) an outcome measure of metabolic syndrome. Odds Ratio (OR) and 95% confidence intervals for metabolic syndrome comparing the highest level of sedentary behaviour to the lowest were extracted for each study. Data were pooled using random effects models to take into account heterogeneity between studies. Ten cross-sectional studies (n = 21393 participants), one high, four moderate and five poor quality, were identified. Greater time spent sedentary increased the odds of metabolic syndrome by 73% (OR 1.73, 95% CI 1.55–1.94, p<0.0001). There were no differences for subgroups of sex, sedentary behaviour measure, metabolic syndrome definition, study quality or country income. There was no evidence of statistical heterogeneity (I2 = 0.0%, p = 0.61) or publication bias (Eggers test t = 1.05, p = 0.32). Conclusions People who spend higher amounts of time in sedentary behaviours have greater odds of having metabolic syndrome. Reducing sedentary behaviours is potentially important for the prevention of metabolic syndrome. PMID:22514690

Adjustment of the dynamic weight distribution as a sensitive parameter for diagnosis of postural alteration in a rodent model of vestibular deficit

PubMed Central

Tighilet, Brahim; Péricat, David; Frelat, Alais; Cazals, Yves; Rastoldo, Guillaume; Boyer, Florent; Dumas, Olivier

2017-01-01

Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken therapeutic actions. To date, the diagnosis methods of posturo-locomotor impairments are restricted to examinations that most often lack sensitivity and precision. In the present work we studied the alterations of the dynamic weight distribution in a rodent model of sudden and complete unilateral vestibular loss. We used a system of force sensors connected to a data analysis system to quantify in real time and in an automated way the weight bearing of the animal on the ground. We show here that sudden, unilateral, complete and permanent loss of the vestibular inputs causes a severe alteration of the dynamic ground weight distribution of vestibulo lesioned rodents. Characteristics of alterations in the dynamic weight distribution vary over time and follow the sequence of appearance and disappearance of the various symptoms that compose the vestibular syndrome. This study reveals for the first time that dynamic weight bearing is a very sensitive parameter for evaluating posturo-locomotor function impairment. Associated with more classical vestibular examinations, this paradigm can considerably enrich the methods for assessing and monitoring vestibular disorders. Systematic application of this type of evaluation to the dizzy or unstable patient could improve the detection of vestibular deficits and allow predicting better their impact on posture and walk. Thus it could also allow a better follow-up of the therapeutic approaches for rehabilitating gait and balance. PMID:29112981

Adjustment of the dynamic weight distribution as a sensitive parameter for diagnosis of postural alteration in a rodent model of vestibular deficit.

PubMed

Tighilet, Brahim; Péricat, David; Frelat, Alais; Cazals, Yves; Rastoldo, Guillaume; Boyer, Florent; Dumas, Olivier; Chabbert, Christian

2017-01-01

Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken therapeutic actions. To date, the diagnosis methods of posturo-locomotor impairments are restricted to examinations that most often lack sensitivity and precision. In the present work we studied the alterations of the dynamic weight distribution in a rodent model of sudden and complete unilateral vestibular loss. We used a system of force sensors connected to a data analysis system to quantify in real time and in an automated way the weight bearing of the animal on the ground. We show here that sudden, unilateral, complete and permanent loss of the vestibular inputs causes a severe alteration of the dynamic ground weight distribution of vestibulo lesioned rodents. Characteristics of alterations in the dynamic weight distribution vary over time and follow the sequence of appearance and disappearance of the various symptoms that compose the vestibular syndrome. This study reveals for the first time that dynamic weight bearing is a very sensitive parameter for evaluating posturo-locomotor function impairment. Associated with more classical vestibular examinations, this paradigm can considerably enrich the methods for assessing and monitoring vestibular disorders. Systematic application of this type of evaluation to the dizzy or unstable patient could improve the detection of vestibular deficits and allow predicting better their impact on posture and walk. Thus it could also allow a better follow-up of the therapeutic approaches for rehabilitating gait and balance.

Where Lies the Fault in Diagnosing Dhat Syndrome among Females? Understanding through a Case Study.

PubMed

Kar, Sujita Kumar; Singh, Amit

2017-01-01

Dhat syndrome is a culture-bound syndrome of South-East Asia, common in young men. However, similar entity has also been described in female patients who attribute their symptoms to nonpathological or physiological vaginal discharge. The current diagnostic system for psychiatric illnesses does not encompass Dhat syndrome in females, and so these group of patients receive alternative diagnoses such as somatoform disorder or depression. As a result of which the focus of unique Dhat syndrome-centered management gets weakened, affecting the clinical outcome. This case study focuses on the diagnostic dilemmas related to Dhat syndrome in females and pitfalls in the current diagnostic system.

Epidemiology of fetal alcohol syndrome in a South African community in the Western Cape Province.

PubMed Central

May, P A; Brooke, L; Gossage, J P; Croxford, J; Adnams, C; Jones, K L; Robinson, L; Viljoen, D

2000-01-01

OBJECTIVES: This study determined the characteristics of fetal alcohol syndrome in a South African community, and methodology was designed for the multidisciplinary study of fetal alcohol syndrome in developing societies. METHODS: An active case ascertainment, 2-tier methodology was used among 992 first-grade pupils. A case-control design, using measures of growth, development, dysmorphology, and maternal risk, delineated characteristics of children with fetal alcohol syndrome. RESULTS: A high rate of fetal alcohol syndrome was found in the schools--40.5 to 46.4 per 1000 children aged 5 to 9 years--and age-specific community rates (ages 6-7) were 39.2 to 42.9. These rates are 18 to 141 times greater than in the United States. Rural residents had significantly more fetal alcohol syndrome. After control for ethnic variation, children with fetal alcohol syndrome had traits similar to those elsewhere: poor growth and development, congruent dysmorphology, and lower intellectual functioning. CONCLUSIONS: This study documented the highest fetal alcohol syndrome rate to date in an overall community population. Fetal alcohol syndrome initiatives that incorporate innovative sampling and active case ascertainment methods can be used to obtain timely and accurate data among developing populations. PMID:11111264

Audiological findings in Noonan syndrome.

PubMed

Tokgoz-Yilmaz, Suna; Turkyilmaz, Meral Didem; Cengiz, Filiz Basak; Sjöstrand, Alev Pektas; Kose, Serdal Kenan; Tekin, Mustafa

2016-10-01

The aim of this study was to evaluate audiologic properties of patients with Noonan syndrome and compare these findings with those of unaffected peers. The study included 17 children with Noonan syndrome and 20 typically developing children without Noonan syndrome. Pure tone and speech audiometry, immitancemetric measurement, otoacoustic emissions measurement and auditory brainstem response tests were applied to all (n = 37) children. Hearing thresholds of children with Noonan syndrome were higher (poorer) than those observed unaffected peers, while the hearing sensitivity of the both groups were normal limits (p = 0.013 for right, p = 0.031 for left ear). Transient evoked otoacoustic emissions amplitudes of the children with Noonan syndrome were lower than the children without Noonan syndrome (p = 0.005 for right, p = 0.002 for left ear). Middle ear pressures and auditory brainstem response values were within normal limits and there was no difference between the two groups (p > 0.05). General benefit of the present study is to characterize the audiologic findings of children with Noonan syndrome, which is beneficial in clinics evaluating children with Noonan syndrome. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Language and Verbal Short-Term Memory Skills in Children with Down Syndrome: A Meta-Analytic Review

ERIC Educational Resources Information Center

Naess, Kari-Anne B.; Lyster, Solveig-Alma Halaas; Hulme, Charles; Melby-Lervag, Monica

2011-01-01

This study presents a meta-analytic review of language and verbal short-term memory skills in children with Down syndrome. The study examines the profile of strengths and weaknesses in children with Down syndrome compared to typically developing children matched for nonverbal mental age. The findings show that children with Down syndrome have…

Divorce in Families of Children with Down Syndrome: A Population-Based Study

ERIC Educational Resources Information Center

Urbano, Richard C.; Hodapp, Robert M.

2007-01-01

In this study, we examined the nature, timing, and correlates of divorce in families of children with Down syndrome (647), other birth defects (10,283) and no identified disability (361,154). Divorce rates among families of children with Down syndrome were lower than in the other two groups. When divorce did occur in the Down syndrome group,…

[Reference value for metabolic syndrome checkup and some problems].

PubMed

Miyake, Noriko

2009-09-01

Metabolic syndrome is one of the most important risk factors of atherosclerotic disease, and visceral obesity is regarded as a principle component of metabolic syndrome. Medical checkups for metabolic syndrome were started in 2008 for the purpose of promoting lifestyle modification through health guidance. The original diagnosis of metabolic syndrome in Japan was presented by the Examination Committee of Criteria for Metabolic Syndrome in April 2005. This guideline defines the waist circumference measurement as an essential component, accompanied by at least two of the following three risk factors: dyslipidemia, a raised blood pressure, and glucose intolerance, and these risk factors were based on multiple representative Japanese cohort studies. However, there are some problems with these standards. For example, it is often the case that accurate evaluation is difficult because variable factors such as meals influence the serum triglyceride level. This influences the reliability of the results of cohort studies. In this symposium, problems with this guideline were presented along with an introduction to the cohort study on which the concept of the syndrome was based. I compiled a cohort study related to metabolic syndrome, and pointed out some problems from the viewpoint of clinical laboratory medicine.

Bilabiate Flowers: The Ultimate Response to Bees?

PubMed Central

Westerkamp, Christian; Claßen-Bockhoff, Regine

2007-01-01

Background and Aims Bilabiate flowers have evolved in many lineages of the angiosperms, thus representing a convincing example of parallel evolution. Similar to keel blossoms, they have obviously evolved in order to protect pollen against pollen-collecting bees. Although many examples are known, a comprehensive survey on floral diversity and functional constraints of bilabiate flowers is lacking. Here, the concept is widened and described as a general pattern. Methods The present paper is a conceptional review including personal observations of the authors. To form a survey on the diversity of bilabiate blossoms, a search was made for examples across the angiosperms and these were combined with personal observations collected during the last 25 years, coupled with knowledge from the literature. New functional terms are introduced that are independent of morphological and taxonomic associations. Key Results Bilabiate constructions occur in at least 38 angiosperm families. They are characterized by dorsiventral organization and dorsal pollen transfer. They are most often realised on the level of a single flower, but may also be present in an inflorescence or as part of a so-called ‘walk-around flower’. Interestingly, in functional terms all nototribic blossoms represent bilabiate constructions. The great majority of specialized bee-flowers can thus be included under bilabiate and keel blossoms. The syndrome introduced here, however, also paves the way for the inclusion of larger animals such as birds and bats. The most important evolutionary trends appear to be in the saving of pollen and the precision of its transfer. With special reference to the Lamiales, selected examples of bilabiate flowers are presented and their functional significance is discussed. Conclusions Bilabiate blossoms protect their pollen against pollen-collecting bees and at the same time render their pollination more precisely. The huge diversity of realised forms indicate the high selection pressure towards the bilabiate syndrome. As bees are very inventive, however, bilabiate constructions will not represent the ultimate response to bees. PMID:17652341

Nutrition: A Primary Therapy in Pediatric Acute Respiratory Distress Syndrome

PubMed Central

Wilson, Bryan; Typpo, Katri

2016-01-01

Appropriate nutrition is an essential component of intensive care management of children with acute respiratory distress syndrome (ARDS) and is linked to patient outcomes. One out of every two children in the pediatric intensive care unit (PICU) will develop malnutrition or have worsening of baseline malnutrition and present with specific micronutrient deficiencies. Early and adequate enteral nutrition (EN) is associated with improved 60-day survival after pediatric critical illness, and, yet, despite early EN guidelines, critically ill children receive on average only 55% of goal calories by PICU day 10. Inadequate delivery of EN is due to perceived feeding intolerance, reluctance to enterally feed children with hemodynamic instability, and fluid restriction. Underlying each of these factors is large practice variation between providers and across institutions for initiation, advancement, and maintenance of EN. Strategies to improve early initiation and advancement and to maintain delivery of EN are needed to improve morbidity and mortality from pediatric ARDS. Both, over and underfeeding, prolong duration of mechanical ventilation in children and worsen other organ function such that precise calorie goals are needed. The gut is thought to act as a “motor” of organ dysfunction, and emerging data regarding the role of intestinal barrier functions and the intestinal microbiome on organ dysfunction and outcomes of critical illness present exciting opportunities to improve patient outcomes. Nutrition should be considered a primary rather than supportive therapy for pediatric ARDS. Precise nutritional therapies, which are titrated and targeted to preservation of intestinal barrier function, prevention of intestinal dysbiosis, preservation of lean body mass, and blunting of the systemic inflammatory response, offer great potential for improving outcomes of pediatric ARDS. In this review, we examine the current evidence regarding dose, route, and timing of nutrition, current recommendations for provision of nutrition to children with ARDS, and the current literature for immune-modulating diets for pediatric ARDS. We will examine emerging data regarding the role of the intestinal microbiome in modulating the response to critical illness. PMID:27790606

Attention in Williams Syndrome and Down's Syndrome: Performance on the New Early Childhood Attention Battery

ERIC Educational Resources Information Center

Breckenridge, Kate; Braddick, Oliver; Anker, Shirley; Woodhouse, Margaret; Atkinson, Janette

2013-01-01

Attentional problems are commonly reported as a feature of the behavioural profile in both Williams syndrome (WS) and Down's syndrome (DS). Recent studies have begun to investigate these impairments empirically, acknowledging the need for an approach that considers cross-syndrome comparisons and developmental changes across the different component…

A novel mutation of the EYA4 gene associated with post-lingual hearing loss in a proband is co-segregating with a novel PAX3 mutation in two congenitally deaf family members.

PubMed

Cesca, Federica; Bettella, Elisa; Polli, Roberta; Cama, Elona; Scimemi, Pietro; Santarelli, Rosamaria; Murgia, Alessandra

2018-01-01

This work was aimed at establishing the molecular etiology of hearing loss in a 9-year old girl with post-lingual non-syndromic mild sensorineural hearing loss with a complex family history of clinically heterogeneous deafness. The proband's DNA was subjected to NGS analysis of a 59-targeted gene panel, with the use of the Ion Torrent PGM platform. Conventional Sanger sequencing was used for segregation analysis in all the affected relatives. The proband and all the other hearing impaired members of the family underwent a thorough clinical and audiological evaluation. A new likely pathogenic mutation in the EYA4 gene (c.1154C > T; p.Ser385Leu) was identified in the proband and in her 42-year-old father with post-lingual non-syndromic profound sensorineural hearing loss. The EYA4 mutation was also found in the proband's grandfather and uncle, both showing clinical features of Waardenburg syndrome type 1. A novel pathogenic splice-site mutation (c.321+1G > A) of the PAX3 gene was found to co-segregate with the EYA4 mutation in these two subjects. The identified novel EYA4 mutation can be considered responsible of the hearing loss observed in the proband and her father, while a dual molecular diagnosis was reached in the relatives co-segregating the EYA4 and the PAX3 mutations. In these two subjects the DFNA10 phenotype was masked by Waardenburg syndrome. The use of NGS targeted gene-panel, in combination with an extensive clinical and audiological examination led us to identify the genetic cause of the hearing loss in members of a family in which different forms of autosomal dominant deafness segregate. These results provide precise and especially important prognostic and follow-up information for the future audiologic management in the youngest affected member. Copyright © 2017 Elsevier B.V. All rights reserved.

Static postural sway of women with and without fibromyalgia syndrome: A cross-sectional study.

PubMed

Trevisan, Deborah Colucci; Driusso, Patricia; Avila, Mariana Arias; Gramani-Say, Karina; Moreira, Fernando Manuel Araujo; Parizotto, Nivaldo Antonio

2017-05-01

There is a frequent complaint about balance problems among fibromyalgia syndrome patients; however, there are not enough studies that have shown static postural sway of women with fibromyalgia syndrome. This study aimed to compare static postural sway of women with and without fibromyalgia syndrome. This is a cross-sectional study in which twenty-nine women with fibromyalgia syndrome and 20 without took part. A posturography evaluation was performed in six different situations (bipedal, right tandem and left tandem, with eyes opened and closed), and questionnaires for clinical depression symptoms, clinical anxiety symptoms, sleep quality, and Visual Analogue Scales for Pain and Fatigue were applied. Mann-Whitney U test was used to check differences among groups; Wilcoxon matched-pair test was used to check differences intragroup; Cohen d coefficient was used to measure effect sizes and Pearson Correlation Coefficient was used for correlations among variables. Level of significance adopted was 5%. Women with fibromyalgia syndrome have presented worse postural sway than women without fibromyalgia syndrome in all situations (P<0.05), and worse scores in all questionnaires (P<0.05). In the eyes closed situations, women with fibromyalgia syndrome presented worse postural sway than women without in the same conditions. Women with fibromyalgia syndrome have worse performance in the static posture test, more prominent in reduced support bases with eyes closed. Pain, fatigue, depression and anxiety may have directly influenced postural sway in fibromyalgia syndrome patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

A study on phenomenology of Dhat syndrome in men in a general medical setting.

PubMed

Prakash, Sathya; Sharan, Pratap; Sood, Mamta

2016-01-01

"Dhat syndrome" is believed to be a culture-bound syndrome of the Indian subcontinent. Although many studies have been performed, many have methodological limitations and there is a lack of agreement in many areas. The aim is to study the phenomenology of "Dhat syndrome" in men and to explore the possibility of subtypes within this entity. It is a cross-sectional descriptive study conducted at a sex and marriage counseling clinic of a tertiary care teaching hospital in Northern India. An operational definition and assessment instrument for "Dhat syndrome" was developed after taking all concerned stakeholders into account and review of literature. It was applied on 100 patients along with socio-demographic profile, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Mini International Neuropsychiatric Interview, and Postgraduate Institute Neuroticism Scale. For statistical analysis, descriptive statistics, group comparisons, and Pearson's product moment correlations were carried out. Factor analysis and cluster analysis were done to determine the factor structure and subtypes of "Dhat syndrome." A diagnostic and assessment instrument for "Dhat syndrome" has been developed and the phenomenology in 100 patients has been described. Both the health beliefs scale and associated symptoms scale demonstrated a three-factor structure. The patients with "Dhat syndrome" could be categorized into three clusters based on severity. There appears to be a significant agreement among various stakeholders on the phenomenology of "Dhat syndrome" although some differences exist. "Dhat syndrome" could be subtyped into three clusters based on severity.

Behavioral phenotypes of genetic syndromes with intellectual disability: comparison of adaptive profiles.

PubMed

Di Nuovo, Santo; Buono, Serafino

2011-10-30

The study of distinctive and consistent behaviors in the most common genetic syndromes with intellectual disability is useful to explain abnormalities or associated psychiatric disorders. The behavioral phenotypes revealed outcomes totally or partially specific for each syndrome. The aim of our study was to compare similarities and differences in the adaptive profiles of the five most frequent genetic syndromes, i.e. Down syndrome, Williams syndrome, Angelman syndrome, Prader-Willi syndrome, and Fragile-X syndrome (fully mutated), taking into account the relation with chronological age and the overall IQ level. The research was carried out using the Vineland Adaptive Behavior Scale (beside the Wechsler Intelligence scales to obtain IQ) with a sample of 181 persons (107 males and 74 females) showing genetic syndromes and mental retardation. Syndrome-based groups were matched for chronological age and mental age (excluding the Angelman group, presenting with severe mental retardation). Similarities and differences in the adaptive profiles are described, relating them to IQs and maladaptive behaviors. The results might be useful in obtaining a global index of adjustment for the assessment of intellectual disability level as well as for educational guidance and rehabilitative plans. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Shift Work Is Associated with Metabolic Syndrome in Young Female Korean Workers.

PubMed

Yu, Kyoung Hwa; Yi, Yu Hyeon; Kim, Yun Jin; Cho, Byung Mann; Lee, Sang Yeoup; Lee, Jeong Gyu; Jeong, Dong Wook; Ji, So Yeon

2017-03-01

Shift work is associated with health problems, including metabolic syndrome. This study investigated the association between shift work and metabolic syndrome in young workers. A total of 3,317 subjects aged 20-40 years enrolled in the 2011-2012 Korean National Health and Nutrition Examination Survey were divided into shift and day workers. We conducted a cross-sectional study and calculated odds ratios using multivariate logistic regression analysis in order to examine the association between shift work and metabolic syndrome. The prevalence of metabolic syndrome was 14.3% and 7.1% among male and female shift workers, respectively. After adjusting for confounding factors, shift work was associated with metabolic syndrome in female workers (odds ratio, 2.53; 95% confidence interval, 1.12 to 5.70). Shift work was associated with metabolic syndrome in young women. Timely efforts are necessary to manage metabolic syndrome in the workplace.

Deficiency neuropathy in wartime: the "paraesthetic-causalgic syndrome" described by Manuel Peraita during the Spanish Civil War.

PubMed

Huertas, Rafael; Del Cura, Maria Isabel

2010-04-08

This paper discusses the contribution of Spanish neurologist Manuel Peraita (1908-1950) to the study of deficiency neuropathy in the setting of the Spanish Civil War (1936-1939). The clinical characteristics of "paraesthetic-causalgic syndrome" or "Madrid syndrome" as described by Peraita are discussed, and the syndrome is presented in relation to other similar conditions, including Strachan's syndrome and burning feet syndrome.

Rapid Prototyping 3D Model in Treatment of Pediatric Hip Dysplasia: A Case Report

PubMed Central

Holt, Andrew M.; Starosolski, Zbigniew; Kan, J. Herman

2017-01-01

Abstract Background: Rapid prototyping is an emerging technology that integrates common medical imaging with specialized production mechanisms to create detailed anatomic replicas. 3D-printed models of musculoskeletal anatomy have already proven useful in orthopedics and their applications continue to expand. Case Description: We present the case of a 10 year-old female with Down syndrome and left acetabular dysplasia and chronic hip instability who underwent periacetabular osteotomy. A rapid prototyping 3D model was created to better understand the anatomy, counsel the family about the problem and the surgical procedure, as well as guide surgical technique. The intricate detail and size match of the model with the patient’s anatomy offered unparalleled, hands-on experience with the patient’s anatomy pre-operatively and improved surgical precision. Conclusions: Our experience with rapid prototyping confirmed its ability to enhance orthopedic care by improving the surgeon’s ability to understand complex anatomy. Additionally, we report a new application utilizing intraoperative fluoroscopic comparison of the model and patient to ensure surgical precision and minimize the risk of complications. This technique could be used in other challenging cases. The increasing availability of rapid prototyping welcomes further use in all areas of orthopedics. PMID:28852351

Combining technologies: a computerized occlusal analysis system synchronized with a computerized electromyography system.

PubMed

Kerstein, Robert B

2004-04-01

Current advances in computer technologies have afforded dentists precision ways to examine occlusal contacts and muscle function. Recently, two separate computer technologies have been synchronized together, so that an operator can record their separate diagnostic data simultaneously. The two systems are: the T Scan II Occlusal Analysis System and the Biopak Electromyography Recording System. The simultaneous recording and playback capacity of these two computer systems allows the operator to analyze and correlate specific occlusal moments to specific electromyographic changes that result from these occlusal moments. This synchronization provides unparalleled evidence of the effect occlusal contact arrangement has on muscle function. Therefore, the occlusal condition of an inserted dental prosthesis or the occlusal scheme of the natural teeth (before and after corrective occlusal adjustments) can be readily evaluated, documented, and quantified for both, quality of occlusal parameters and muscle activity and the responses to the quality of the occlusal condition. This article describes their synchronization and illustrates their use in performing precision occlusal adjustment procedures on two patients: one who demonstrates occlusal disharmony while exhibiting the signs and symptoms of chronic myofascial pain dysfunction syndrome, and the other who had extensive restorative work accomplished but exhibits occlusal discomfort post-operatively.

Qualitative and Quantitative Analysis of the Major Constituents in Chinese Medical Preparation Lianhua-Qingwen Capsule by UPLC-DAD-QTOF-MS

PubMed Central

Jia, Weina; Wang, Chunhua; Wang, Yuefei; Pan, Guixiang; Jiang, Miaomiao; Li, Zheng; Zhu, Yan

2015-01-01

Lianhua-Qingwen capsule (LQC) is a commonly used Chinese medical preparation to treat viral influenza and especially played a very important role in the fight against severe acute respiratory syndrome (SARS) in 2002-2003 in China. In this paper, a rapid ultraperformance liquid chromatography coupled with diode-array detector and quadrupole time-of-flight mass spectrometry (UPLC-DAD-QTOF-MS) method was established for qualitative and quantitative analysis of the major constituents of LQC. A total of 61 compounds including flavonoids, phenylpropanoids, anthraquinones, triterpenoids, iridoids, and other types of compounds were unambiguously or tentatively identified by comparing the retention times and accurate mass measurement with reference compounds or literature data. Among them, twelve representative compounds were further quantified as chemical markers in quantitative analysis, including salidroside, chlorogenic acid, forsythoside E, cryptochlorogenic acid, amygdalin, sweroside, hyperin, rutin, forsythoside A, phillyrin, rhein, and glycyrrhizic acid. The UPLC-DAD method was evaluated with linearity, limit of detection (LOD), limit of quantification (LOQ), precision, stability, repeatability, and recovery tests. The results showed that the developed quantitative method was linear, sensitive, and precise for the quality control of LQC. PMID:25654135

Rapid Prototyping 3D Model in Treatment of Pediatric Hip Dysplasia: A Case Report.

PubMed

Holt, Andrew M; Starosolski, Zbigniew; Kan, J Herman; Rosenfeld, Scott B

2017-01-01

Rapid prototyping is an emerging technology that integrates common medical imaging with specialized production mechanisms to create detailed anatomic replicas. 3D-printed models of musculoskeletal anatomy have already proven useful in orthopedics and their applications continue to expand. We present the case of a 10 year-old female with Down syndrome and left acetabular dysplasia and chronic hip instability who underwent periacetabular osteotomy. A rapid prototyping 3D model was created to better understand the anatomy, counsel the family about the problem and the surgical procedure, as well as guide surgical technique. The intricate detail and size match of the model with the patient's anatomy offered unparalleled, hands-on experience with the patient's anatomy pre-operatively and improved surgical precision. Our experience with rapid prototyping confirmed its ability to enhance orthopedic care by improving the surgeon's ability to understand complex anatomy. Additionally, we report a new application utilizing intraoperative fluoroscopic comparison of the model and patient to ensure surgical precision and minimize the risk of complications. This technique could be used in other challenging cases. The increasing availability of rapid prototyping welcomes further use in all areas of orthopedics.

Fluorescence anisotropy (polarization): from drug screening to precision medicine

PubMed Central

Zhang, Hairong; Wu, Qian; Berezin, Mikhail Y.

2016-01-01

Introduction Fluorescence anisotropy (FA) is one of the major established methods accepted by industry and regulatory agencies for understanding the mechanisms of drug action and selecting drug candidates utilizing a high-throughput format. Areas covered This review covers the basics of FA and complementary methods, such as fluorescence lifetime anisotropy and their roles in the drug discovery process. The authors highlight the factors affecting FA readouts, fluorophore selection, and instrumentation. Furthermore, the authors describe the recent development of a successful, commercially valuable FA assay for Long QT syndrome drug toxicity to illustrate the role that FA can play in the early stages of drug discovery. Expert opinion Despite the success in drug discovery, the FA-based technique experiences competitive pressure from other homogeneous assays. That being said, FA is an established yet rapidly developing technique, recognized by academic institutions, the pharmaceutical industry, and regulatory agencies across the globe. The technical problems encountered in working with small molecules in homogeneous assays are largely solved, and new challenges come from more complex biological molecules and nanoparticles. With that, FA will remain one of the major work-horse techniques leading to precision (personalized) medicine. PMID:26289575

Selenium intake and metabolic syndrome: A systematic review.

PubMed

Retondario, Anabelle; Fernandes, Ricardo; Rockenbach, Gabriele; Alves, Mariane de Almeida; Bricarello, Liliana Paula; Trindade, Erasmo Benicio Santos de Moraes; Vasconcelos, Francisco de Assis Guedes de

2018-03-02

Metabolic syndrome is a multi-causal disease. Its treatment includes lifestyle changes with a focus on weight loss. This systematic review assessed the association between Selenium intake and metabolic syndrome. Data were collected mainly from four databases: PubMed, CENTRAL (Cochrane), Scopus and Web of Knowledge. Keywords related to metabolic syndrome, selenium, as well as metabolic syndrome features were searched. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. A systematic review protocol was registered at PROSPERO (n. 42016046321). Two reviewers independently screened 2957 abstracts. Six studies were included to perform data extraction with standardized spreadsheets. The risk of bias was assessed by using specific tools according to the design of the relevant studies. An assessment was carried out based on the appropriateness of the study reports accordingly to STROBE and the CONSORT-based checklist for each study design. Three studies found no association between Selenium intake and metabolic syndrome; two of them found an inverse association; and one study found a direct association between Selenium intake and metabolic syndrome. One study also showed an inverse association between Selenium intake and the prevalence of high waist circumference, high diastolic blood pressure, and hyperglycaemia in women. Overall, based on the argumentation and results of this study, it is possible to conclude that Selenium intake and metabolic syndrome are not clearly associated in adults and elderly. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Lifestyle and Risk of Chronic Prostatitis/Chronic Pelvic Pain Syndrome in a Cohort of United States Male Health Professionals

PubMed Central

Zhang, Ran; Sutcliffe, Siobhan; Giovannucci, Edward; Willett, Walter C.; Platz, Elizabeth A.; Rosner, Bernard A.; Dimitrakoff, Jordan D.; Wu, Kana

2015-01-01

Purpose Although chronic prostatitis/chronic pelvic pain syndrome is a prevalent urological disorder among men of all ages, its etiology remains unknown. Only a few previous studies have examined associations between lifestyle factors and chronic prostatitis/chronic pelvic pain syndrome, of which most were limited by the cross-sectional study design and lack of control for possible confounders. To address these limitations we performed a cohort study of major lifestyle factors (obesity, smoking and hypertension) and chronic prostatitis/chronic pelvic pain syndrome risk in the HPFS (Health Professionals Follow-up Study), a large ongoing cohort of United States based male health professionals. Materials and Methods The HPFS includes 51,529 men who were 40 to 75 years old at baseline in 1986. At enrollment and every 2 years thereafter participants have completed questionnaires on lifestyle and health conditions. In 2008 participants completed an additional set of questions on recent chronic prostatitis/chronic pelvic pain syndrome pain symptoms modified from the NIH (National Institutes of Health)-CPSI (Chronic Prostatitis Symptom Index) as well as questions on approximate date of symptom onset. The 653 participants with NIH-CPSI pain scores 8 or greater who first experienced symptoms after 1986 were considered incident chronic prostatitis/chronic pelvic pain syndrome cases and the 19,138 who completed chronic prostatitis/chronic pelvic pain syndrome questions but did not report chronic prostatitis/chronic pelvic pain syndrome related pain were considered noncases. Results No associations were observed for baseline body mass index, waist circumference, waist-to-hip ratio, cigarette smoking and hypertension with chronic prostatitis/chronic pelvic pain syndrome risk (each OR ≤1.34). Conclusions In this large cohort study none of the lifestyle factors examined was associated with chronic prostatitis/chronic pelvic pain syndrome risk. As the etiology of chronic prostatitis/chronic pelvic pain syndrome remains unknown, additional prospective studies are needed to elucidate modifiable risk factors for this common condition. PMID:26070893

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

[Analysis of 115 kidney biopsies performed in Dakar (Senegal)].

PubMed

Diouf, B; Ka, E F; Niang, A; Mbengue, M; Ka, M M; Diouf, M L; Pouye, A; Moreira-Diop, T

2001-01-01

Few data are now avalable concerning renal pathology in black African. That is why we under took this study as a contribution to the better knowlege of pathological aspects of kidney disease in Dakar by analysing our 6 years's experience. It was a retrospective study concerning all the patients who underwent renal biopsyfrom January 1993 to December 1998. The samples were studied on light microscopy and immunoflorescence at the nephrology unit of Necker Hospital in Paris. We performed 115 renal biopsies during this period conceming 64 males and 51 females from 5 to 60 years old (mean age 28 years). Nephrotic syndrome represented 67% of the indications, followed by lupus nephritis (13%). We found primary glomerulonephritis in 75% of all cases. Anatomicaly, 54 cases of focal and segmental hyalinosis were found (47% of all biopsies). The other lesions were extra-membranous glomerulonephritis (8,6%), minimal change glomerulonephritis 6%, endo and extra-capillary glomerulonephritis 2,6%, Mesangial glomerulonephrits, extra-capillary glomerunephrotis, IgA nephropaty represented each 1,7%. In 5% of cases the lesions did not permit a precise classification. Focal and segmental hyalinosis is the main primary lesion and lupus nephritis the main secondary one in kidney deseases biopsied in Dakar.

Fetuses with Down's Syndrome detected by prenatal screening are more likely to abort spontaneously than fetuses with Down's Syndrome not detected by prenatal screening.

PubMed

Leporrier, Nathalie; Herrou, Michel; Morello, Rémy; Leymarie, Pierre

2003-01-01

Pregnancy with Down's Syndrome is often terminated by miscarriage. We have investigated whether prenatal screening would lead preferentially to the identification of fetuses with Down's Syndrome prone to abort spontaneously. A comparison between the observed and the expected decrease in the prevalence of Down's Syndrome at term following extensive prenatal screening. A study from 1990 to 1998 in a limited and well controlled area of western France (Basse Normandie), with a birth rate close to 20,000 a year. Women under 38 years of age among whom prenatal screening for Down's Syndrome using biochemical tests and ultrasound findings became progressively extensive in this era. Our study was based on the registration of Down's Syndrome cases detected prenatally from screening, and live births with Down's Syndrome. Fetal loss rate in the population of prenatally detectable Down's Syndrome was evaluated by comparing the increase in detection of cases of Down's Syndrome following prenatal screening with the expected decrease in the number of cases of Down's Syndrome at birth. The results obtained were compared with published data on the rates of fetal losses postulated to occur among fetuses with Down's Syndrome. Comparison of the potential fetal loss rate in a population in whom Down's Syndrome was detected prenatally with the expected fetal loss rate of unselected ones. Prenatal screening resulted in a significant (42%) decrease (P < 0.001) in the prevalence at term of the disorder. Among the 53 fetuses with Down's Syndrome detected prenatally during the last three years of the study, about 50% would have aborted spontaneously if the pregnancy had been allowed to continue. This figure was significantly higher (P < 0.002) than expected on the basis of results from the literature, indicating that current estimates of miscarriage rates among fetuses with Down's Syndrome do not apply to the selected group of cases detectable from prenatal screening. Our results suggest that fetuses with Down's Syndrome detectable prenatally from screening are more likely to abort spontaneously than fetuses with Down's Syndrome which are not detected.

Extracorporeal membrane oxygenation in children with heart disease and down syndrome: a multicenter analysis.

PubMed

Gupta, Punkaj; Gossett, Jeffrey M; Rycus, Peter T; Prodhan, Parthak

2014-12-01

The data on the outcomes of children with heart disease and Down syndrome receiving extracorporeal membrane oxygenation (ECMO) for cardiac or respiratory failure are limited. This study aimed to evaluate morbidity and mortality associated with ECMO in children with Down syndrome and heart disease. Children younger than 18 years undergoing heart surgery and ECMO reported in the Extracorporeal Life Support Organization (ELSO) registry (1998-2011) were included in the study. The registry was queried for the following five heart defects: common atrioventricular (AV) canal, tetralogy of Fallot, truncus arteriosus, transposition of great vessels, and interrupted aortic arch. Data collection included patient characteristics, ECMO characteristics, and outcomes. The outcomes evaluated included mortality, ECMO duration, and length of hospital stay for patients with Down syndrome and those with no Down syndrome. The study enrolled 2,815 patients qualified for inclusion. Of these patients, 121 had Down syndrome, whereas 2,694 had no genetic syndrome and were included in the control group. The median age of the patients was 45 days (interquartile range [IQR] 9-192 days), and the median weight was 3.8 kg (IQR 3.0-6.1 kg). The most common cardiac defects in Down syndrome group were common AV canal (63 %) and tetralogy of Fallot (40 %). The Down syndrome group included older patients with greater body weight than the control group. The mortality rate was lower in the Down syndrome group than in the control group (44 vs. 56 %; p = 0.01). The duration of ECMO and length of hospital stay were similar in the two groups. The findings showed that ECMO can be used for children with heart disease and Down syndrome with good results. The outcomes were comparable between the children with Down syndrome and the children without Down syndrome.

A TWIN STUDY OF SCHIZOAFFECTIVE-MANIA, SCHIZOAFFECTIVE-DEPRESSION AND OTHER PSYCHOTIC SYNDROMES

PubMed Central

Cardno, Alastair G; Rijsdijk, Frühling V; West, Robert M; Gottesman, Irving I; Craddock, Nick; Murray, Robin M; McGuffin, Peter

2012-01-01

The nosological status of schizoaffective disorders remains controversial. Twin studies are potentially valuable for investigating relationships between schizoaffective-mania, schizoaffective-depression and other psychotic syndromes, but no such study has yet been reported. We ascertained 224 probandwise twin pairs (106 monozygotic, 118 same-sex dizygotic), where probands had psychotic or manic symptoms, from the Maudsley Twin Register in London (1948–1993). We investigated Research Diagnostic Criteria schizoaffective-mania, schizoaffective-depression, schizophrenia, mania and depressive psychosis primarily using a non-hierarchical classification, and additionally using hierarchical and data-derived classifications, and a classification featuring broad schizophrenic and manic syndromes without separate schizoaffective syndromes. We investigated inter-rater reliability and co-occurrence of syndromes within twin probands and twin pairs. The schizoaffective syndromes showed only moderate inter-rater reliability. There was general significant co-occurrence between syndromes within twin probands and monozygotic pairs, and a trend for schizoaffective-mania and mania to have the greatest co-occurrence. Schizoaffective syndromes in monozygotic probands were associated with relatively high risk of a psychotic syndrome occurring in their co-twins. The classification of broad schizophrenic and manic syndromes without separate schizoaffective syndromes showed improved inter-rater reliability, but high genetic and environmental correlations between the two broad syndromes. The results are consistent with regarding schizoaffective-mania as due to co-occurring elevated liability to schizophrenia, mania and depression; and schizoaffective-depression as due to co-occurring elevated liability to schizophrenia and depression, but with less elevation of liability to mania. If in due course schizoaffective syndromes show satisfactory inter-rater reliability and some specific etiological factors they could alternatively be regarded as partly independent disorders. PMID:22213671

A twin study of schizoaffective-mania, schizoaffective-depression, and other psychotic syndromes.

PubMed

Cardno, Alastair G; Rijsdijk, Frühling V; West, Robert M; Gottesman, Irving I; Craddock, Nick; Murray, Robin M; McGuffin, Peter

2012-03-01

The nosological status of schizoaffective disorders remains controversial. Twin studies are potentially valuable for investigating relationships between schizoaffective-mania, schizoaffective-depression, and other psychotic syndromes, but no such study has yet been reported. We ascertained 224 probandwise twin pairs [106 monozygotic (MZ), 118 same-sex dizygotic (DZ)], where probands had psychotic or manic symptoms, from the Maudsley Twin Register in London (1948-1993). We investigated Research Diagnostic Criteria schizoaffective-mania, schizoaffective-depression, schizophrenia, mania and depressive psychosis primarily using a non-hierarchical classification, and additionally using hierarchical and data-derived classifications, and a classification featuring broad schizophrenic and manic syndromes without separate schizoaffective syndromes. We investigated inter-rater reliability and co-occurrence of syndromes within twin probands and twin pairs. The schizoaffective syndromes showed only moderate inter-rater reliability. There was general significant co-occurrence between syndromes within twin probands and MZ pairs, and a trend for schizoaffective-mania and mania to have the greatest co-occurrence. Schizoaffective syndromes in MZ probands were associated with relatively high risk of a psychotic syndrome occurring in their co-twins. The classification of broad schizophrenic and manic syndromes without separate schizoaffective syndromes showed improved inter-rater reliability, but high genetic and environmental correlations between the two broad syndromes. The results are consistent with regarding schizoaffective-mania as due to co-occurring elevated liability to schizophrenia, mania, and depression; and schizoaffective-depression as due to co-occurring elevated liability to schizophrenia and depression, but with less elevation of liability to mania. If in due course schizoaffective syndromes show satisfactory inter-rater reliability and some specific etiological factors they could alternatively be regarded as partly independent disorders. Copyright © 2011 Wiley Periodicals, Inc.

Is the metabolic syndrome a "small baby" syndrome?: the bogalusa heart study.

PubMed

Harville, Emily W; Srinivasan, Sathanur; Chen, Wei; Berenson, Gerald S

2012-12-01

Metabolic syndrome has been called a "small baby syndrome," but other analyses suggest that postnatal growth is more important than birthweight, or that large babies are also at risk. The aim of this analysis was to examine whether there was a relationship between both low and high birthweight and metabolic syndrome, using multiple definitions of metabolic syndrome, and to determine whether this relationship varied by body size across the life course. Data from the Bogalusa Heart Study, a study of cardiovascular disease in children and young adults, were linked to birth certificate data. Metabolic syndrome was defined by the National Cholesterol Education Program, the International Diabetes Foundation, and the World Health Organization (WHO) definition. Small-for-gestational-age (SGA) was defined as birthweight <10(th) percentile by sex for gestational age and large-for-gestational-age (LGA) as birthweight >90(th) percentile. Birthweight-for-gestational-age was also examined as a continuous predictor. Chi-squared tests and logistic regression were used to examine the relationship between birth size and metabolic syndrome. Higher birthweight-for-gestational-age was associated with a reduced risk of metabolic syndrome, especially by the WHO definition. After adjustment for body mass index (BMI), categorized birthweight was associated with metabolic syndrome, with the protective associations with LGA being stronger than the positive associations with SGA. Among the individual components of metabolic syndrome, higher waist circumference was associated with both SGA and LGA after BMI was controlled for. Effects of SGA and BMI at any age were largely independent rather than interactive. SGA is associated with some, but not all, components of metabolic syndrome. The relationship between SGA and metabolic syndrome is partially confounded by later BMI.

Polycystic ovary syndrome throughout a woman's life.

PubMed

Bellver, José; Rodríguez-Tabernero, Luis; Robles, Ana; Muñoz, Elkin; Martínez, Francisca; Landeras, José; García-Velasco, Juan; Fontes, Juan; Álvarez, Mónica; Álvarez, Claudio; Acevedo, Belén

2018-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women and the main cause of infertility due to anovulation. However, this syndrome spans the lives of women affecting them from in-utero life until death, leading to several health risks that can impair quality of life and increase morbidity and mortality rates. Fetal programming may represent the beginning of the condition characterized by hyperandrogenism and insulin resistance which leads to a series of medical consequences in adolescence, adulthood, and old age. Menstrual and fertility problems evolve into metabolic complications as age advances. An early and precise diagnosis is important for an adequate management of PCOS, especially at the extreme ends of the reproductive lifespan. However, many different phenotypes are included under the same condition, being important to look at these different phenotypes separately, as they may require different treatments and have different consequences. In this way, PCOS exhibits a great metabolic complexity and its diagnosis needs to be revised once again and adapted to recent data obtained by new technologies. According to the current medical literature, lifestyle therapy constitutes the first step in the management, especially when excess body weight is associated. Pharmacotherapy is frequently used to treat the most predominant manifestations in each age group, such as irregular menses and hirsutism in adolescence, fertility problems in adulthood, and metabolic problems and risk of cancer in old age. Close surveillance is mandatory in each stage of life to avoid health risks which may also affect the offspring, since fetal and post-natal complications seem to be increased in PCOS women.

Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

PubMed Central

Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

2014-01-01

Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

Viral Heart Disease and Acute Coronary Syndromes - Often or Rare Coexistence?

PubMed

Pawlak, Agnieszka; Wiligorska, Natalia; Wiligorska, Diana; Frontczak-Baniewicz, Malgorzata; Przybylski, Maciej; Krzyzewski, Rafal; Ziemba, Andrzej; Gil, Robert J

2018-01-01

Clinical presentation of viral myocarditis can mimic acute coronary syndrome and making diagnosis of viral heart disease (VHD) may be challenging. The presence of coronary artery disease (CAD) does not always exclude VHD and these entities can coexist. However, the incidence of co-occurrence of CAD and VHD is not precisely known. Moreover, inflammatory process caused by viruses may result in atherosclerotic plaque destabilization. The goal of this work is to summarize the current knowledge about co-occurrence of VHD and CAD. This article presents the importance of inflammatory process in both diseases and helps to understand pathophysiological mechanisms underlying their coexistence. It provides information about making differential diagnosis between these entities, including clinical presentation, noninvasive imaging features and findings in endomyocardial biopsy. Although currently there are no standard therapy strategies in coexistence of VHD and CAD, we present some remarkable aspects of treatment of patients, in whom VHD co-occurs with CAD. Viral heart disease may occur both in patients without and with atherosclerotic plaques in coronary arteries. Destabilization of atherosclerotic plaques in coronary arteries can be facilitated by inflammatory process. Increased inflammatory infiltrates in the coronary lesions of patients with VHD can lead to plaques' instability and consequently trigger acute coronary syndrome. In this article we attempted to present that co-occurrence of VHD and CAD may have therapeutic implications and as specific antiviral treatment is currently available, proper diagnosis and treatment can improve patient's condition and prognosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Divorce in families of children with Down Syndrome or Rett Syndrome.

PubMed

Lederman, Vivian Renne Gerber; Alves, Bianca dos Santos; Negrão, Juliana; Maria, Juliana Negrão; Schwartzman, José Salomão; D'Antino, Maria Eloisa Famá; Brunoni, Decio

2015-05-01

This study evaluates the impact in the stability and management of the marriage of parents of a child with Down or Rett Syndrome. Morbidity of the syndromes and the marital status of the couples before and after the birth of the affected children were considered variables. The divorce rate in families with Down syndrome was 10%, similar to the Brazilian rate population. In Rett Syndrome, the divorce rate was significantly higher, 23.5%. The higher morbidity of Rett Syndrome, and the moment of diagnosis could be relevant factors for the increased divorce rate related to this syndrome.

Perceived motor problems in daily life: Focus group interviews with people with Noonan syndrome and their relatives.

PubMed

Croonen, Ellen A; Harmsen, Mirjam; Van der Burgt, Ineke; Draaisma, Jos M; Noordam, Kees; Essink, Marlou; Nijhuis-van der Sanden, Maria W G

2016-09-01

Studies from a patient perspective on motor performance problems in Noonan syndrome in daily life are lacking. The aims of this study were to provide insight into the motor performance problems that people with Noonan syndrome and/or their relatives experienced, the major consequences they suffered, the benefits of interventions they experienced, and the experiences with healthcare professionals they mentioned. We interviewed 10 adults with Noonan syndrome (two were joined by their parent), and 23 mothers (five of whom had Noonan syndrome), nine fathers (one of whom had Noonan syndrome) and one cousin who reported on 28 children with Noonan syndrome. People with Noonan syndrome reported particular problems related to pain, decreased muscle strength, fatigue, and clumsiness, which had an evident impact on functioning in daily life. Most participants believed that problems with motor performance improved with exercise, appropriate physiotherapy guidance, and other supportive interventions. Nevertheless, people with Noonan syndrome and/or their relatives did not feel heard and supported and experienced no understanding of their problems by healthcare professionals. This was the first study from a patient perspective that described the motor performance problems in people with Noonan syndrome, the major consequences in daily life, the positive experiences of interventions and the miscommunication with healthcare professionals. To achieve optimal support, healthcare professionals, as well as people with Noonan syndrome and/or their relatives themselves, should be aware of these frequently presented problems with motor performance. Research on these different aspects is needed to better understand and support people with Noonan syndrome.© 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Long-term memory for verbal and visual information in Down syndrome and Williams syndrome: performance on the Doors and People test.

PubMed

Jarrold, Christopher; Baddeley, Alan D; Phillips, Caroline

2007-02-01

Previous studies have suggested that Williams syndrome and Down syndrome may be associated with specific short-term memory deficits. Individuals with Williams syndrome perform relatively poorly on tests of visuo-spatial short-term memory and individuals with Down syndrome show a relative deficit on verbal short-term memory tasks. However, these patterns of impairments may reflect the impact of generally impaired visuo-spatial processing skills in Williams syndrome, and verbal abilities in Down syndrome. The current study explored this possibility by assessing long-term memory among 15 individuals with Williams syndrome and 20 individuals with Down syndrome using the Doors and People test, a battery which assesses recall and recognition of verbal and visual information. Individuals' performance was standardised for age and level of intellectual ability with reference to that shown by a sample of 110 typically developing children. The results showed that individuals with Down syndrome have no differential deficits in long-term memory for verbal information, implying that verbal short-term memory deficits in this population are relatively selective. Instead both individuals with Down syndrome and with Williams syndrome showed some evidence of relatively poor performance on tests of long-term memory for visual information. It is therefore possible that visuo-spatial short-term memory deficits that have previously been demonstrated in Williams syndrome may be secondary to more general problems in visuo-spatial processing in this population.

Hip abductor strength and lower extremity running related injury in distance runners: A systematic review.

PubMed

Mucha, Matthew D; Caldwell, Wade; Schlueter, Emily L; Walters, Carly; Hassen, Amy

2017-04-01

Determine the association between hip abduction strength and lower extremity running related injury in distance runners. Systematic review. Prospective longitudinal and cross sectional studies that quantified hip abduction strength and provided diagnosis of running related injury in distance runners were included and assessed for quality. Effect size was calculated for between group differences in hip abduction strength. Of the 1841 articles returned in the initial search, 11 studies matched all inclusion criteria. Studies were grouped according to injury: iliotibial band syndrome, patellofemoral pain syndrome, medial tibial stress syndrome, tibial stress fracture, and Achilles tendinopathy, and examined for strength differences between injured and non-injured groups. Meaningful differences were found in the studies examining iliotibial band syndrome. Three of five iliotibial band syndrome articles found weakness in runners with iliotibial band syndrome; two were of strong methodological rigor and both of those found a relationship between weakness and injury. Other results did not form associative or predictive relationships between weakness and injury in distance runners. Hip abduction weakness evaluated by hand held dynamometer may be associated with iliotibial band syndrome in distance runners as suggested by several cross sectional studies but is unclear as a significant factor for the development of patellofemoral pain syndrome, medial tibial stress syndrome, tibial stress fracture or Achilles tendinopathy according to the current literature. Future studies are needed with consistent methodology and inclusion of all distance running populations to determine the significance of hip abduction strength in relationship to lower extremity injury. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Metabolic syndrome correlates poorly with cognitive performance in stroke-free community-dwelling older adults: a population-based, cross-sectional study in rural Ecuador.

PubMed

Del Brutto, Oscar H; Mera, Robertino M; Zambrano, Mauricio

2016-04-01

Studies investigating a possible correlation between metabolic syndrome and cognitive decline have been inconsistent. To determine whether metabolic syndrome or each of its components correlate with cognitive performance in community-dwelling older adults in rural Ecuador. Stroke-free Atahualpa residents aged ≥60 years were identified during a door-to-door survey. Metabolic syndrome was defined according to the International Diabetes Federation criteria. Cognition was evaluated by the use of the Montreal Cognitive Assessment (MoCA). Multivariate logistic regression models estimated the association between metabolic syndrome and each of its components with cognitive performance. A total of 212 persons (mean age: 69.2 ± 7.2 years, 64 % women) were enrolled. Of these, 120 (57 %) had metabolic syndrome. Mean scores in the MoCA were 18.2 ± 4.6 for persons with and 19 ± 4.7 for those without metabolic syndrome. In fully adjusted logistic models, MoCA scores were not associated with metabolic syndrome (p = 0.101). After testing individual components of metabolic syndrome with the MoCA score, we found that only hypertriglyceridemia was independently associated with the MoCA score (p = 0.009). This population-based study showed a poor correlation of metabolic syndrome with cognitive performance after adjusting for relevant confounders. Of the individual components of metabolic syndrome, only hypertriglyceridemia correlated with worse cognitive performance.

Prevalence of Burnout Syndrome in patients admitted with acute coronary syndrome.

PubMed

Prosdócimo, Ana Cláudia Giaxa; Lucina, Luciane Boreki; Marcia, Olandoski; Jobs, Priscila Megda João; Schio, Nicolle Amboni; Baldanzi, Fernanda Fachin; Costantini, Costantino Ortiz; Benevides-Pereira, Ana Maria Teresa; Guarita-Souza, Luiz Cesar; Faria-Neto, José Rocha

2015-03-01

Burnout Syndrome is the extreme emotional response to chronic occupational stress, manifesting as physical and mental exhaustion. Although associated with higher prevalence of cardiovascular risk factors, no study so far has evaluated whether the Burnout Syndrome could be a prevalent factor in non-elderly individuals active in the labor market, admitted for acute coronary syndrome (ACS). To evaluate the prevalence of the Burnout Syndrome in non-elderly, economically active patients, hospitalized with ACS. Cross-sectional study conducted in a tertiary and private cardiology center, with economically active patients aged <65 years, hospitalized with diagnosis of ACS. The Burnout Syndrome was evaluated with the Burnout Syndrome Inventory (BSI), which assesses workplace conditions and four dimensions that characterize the syndrome: emotional exhaustion (EE), emotional distancing (EmD), dehumanization (De) and professional fulfillment (PF). The Lipp's Stress Symptoms Inventory for Adults (LSSI) was applied to evaluate global stress. Of 830 patients evaluated with suspected ACS, 170 met the study criteria, 90% of which were men, overall average age was 52 years, and 40.5% had an average income above 11 minimum wages. The prevalence of the Burnout Syndrome was 4.1%. When we evaluated each dimension individually, we found high EE in 34.7%, high De in 52.4%, high EDi in 30.6%, and low PF in 5.9%. The overall prevalence of stress was 87.5%. We found a low prevalence of Burnout Syndrome in an economically active, non-elderly population among patients admitted for ACS in a tertiary and private hospital.

Measuring Use and Cost of Health Sector and Related Care in a Population of Girls and Young Women with Rett Syndrome

ERIC Educational Resources Information Center

Hendrie, Delia; Bebbington, Ami; Bower, Carol; Leonard, Helen

2011-01-01

This study measured use and cost of health sector and related services in Rett syndrome and effects of socio-demographic, clinical severity and genetic factors on costs. The study population consisted of individuals with Rett syndrome registered with the Australian Rett Syndrome Database in 2004. Descriptive analysis was used to examine patterns…

Pathways to Language: A Naturalistic Study of Children with Williams Syndrome and Children with Down Syndrome

ERIC Educational Resources Information Center

Levy, Yonata; Eilam, Ariela

2013-01-01

This is a naturalistic study of the development of language in Hebrew-speaking children with Williams syndrome (WS) and children with Down syndrome (DS), whose MLU extended from 1[multiplied by]0 to 4[multiplied by]4. Developmental curves over the entire span of data collection revealed minor differences between children with WS, children with DS,…

Reclassification of clinical sleep disorders using traditional models of syndromic, neuroanatomic, pathophysiological and etiological diagnosis.

PubMed

Spitzer, A Robert

2014-09-01

Existing classifications of central nervous system sleep disorders do not often provide tools to diagnose the majority of patients complaining of sleep-related symptoms, nor always guide effective treatment. I present a novel classification system that completely separates clinical syndromes from anatomical localization, pathophysiology, and etiology. The clinical syndrome I present can describe the majority of patients, but can be fractionated into individual subgroups for further study. By then separating the anatomy and physiology from the symptoms, an avenue of research becomes available to study the different possible structures that regulate sleep, that may be damaged and cause syndromes of sleep dysfunction. Some of these may produce symptoms that overlap with narcolepsy and some may be distinct. Because the clinical syndrome should be distinguished from anatomy or physiology, I have proposed the term narcoleptiform syndrome for the clinical syndrome. The model also clearly separates etiology from anatomy in a classical neurological manner. This allows etiology, localization and symptoms to be studied separately. It is likely that different etiologies may produce damage in areas that produce similar syndromes. For example, in this model, different causes of damage to the orexin nucleus would result in the same clinical syndrome. This reinforces the concept of studying anatomy, symptoms and etiology separately. By studying the relationship of syndromes or symptoms to anatomic localization and pathophysiology, it should be possible to test novel approaches to treatment based on different underlying structure or function. For example, patients with lesions in the ventrolateral preoptic nucleus or the thalamic intralaminar nuclei may both present with insomnia symptoms but need different treatment; or they might present with symptoms overlapping narcolepsy (a narcoleptiform syndrome) yet need different treatment. In some cases, a single treatment may cross over more than one location, and the best predictor might be symptoms. These are issues that need to undergo careful study on a syndromic, anatomic and physiological bases. This novel model opens up new avenues for understanding central nervous system sleep disorders, providing testable hypotheses regarding diagnosis and treatment. Copyright © 2014 The Author. Published by Elsevier Ltd.. All rights reserved.

Neuroimaging of Central Sensitivity Syndromes: Key Insights from the Scientific Literature

PubMed Central

Walitt, Brian; Čeko, Marta; Gracely, John L.; Gracely, Richard H.

2016-01-01

Central sensitivity syndromes are characterized by distressing symptoms, such as pain and fatigue, in the absence of clinically obvious pathology. The scientific underpinnings of these disorders are not currently known. Modern neuroimaging techniques promise new insights into mechanisms mediating these postulated syndromes. We review the results of neuroimaging applied to five central sensitivity syndromes: fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint disorder, and vulvodynia syndrome. Neuroimaging studies of basal metabolism, anatomic constitution, molecular constituents, evoked neural activity, and treatment effect are compared across all of these syndromes. Evoked sensory paradigms reveal sensory augmentation to both painful and non-painful stimulation. This is a transformative observation for these syndromes, which were historically considered to be completely of hysterical or feigned in origin. However, whether sensory augmentation represents the cause of these syndromes, a predisposing factor, an endophenotype, or an epiphenomenon cannot be discerned from the current literature. Further, the result from cross-sectional neuroimaging studies of basal activity, anatomy, and molecular constituency are extremely heterogeneous within and between the syndromes. A defining neuroimaging “signature” cannot be discerned for any of the particular syndromes or for an over-arching central sensitization mechanism common to all of the syndromes. Several issues confound initial attempts to meaningfully measure treatment effects in these syndromes. At this time, the existence of “central sensitivity syndromes” is based more soundly on clinical and epidemiological evidence. A coherent picture of a “central sensitization” mechanism that bridges across all of these syndromes does not emerge from the existing scientific evidence. PMID:26717948

Six controversial issues on subclinical Cushing's syndrome.

PubMed

Chiodini, Iacopo; Albani, Adriana; Ambrogio, Alberto Giacinto; Campo, Michela; De Martino, Maria Cristina; Marcelli, Giorgia; Morelli, Valentina; Zampetti, Benedetta; Colao, Annamaria; Pivonello, Rosario

2017-05-01

Subclinical Cushing's syndrome is a condition of hypercortisolism in the absence of signs specific of overt cortisol excess, and it is associated with an increased risk of diabetes, hypertension, fragility fractures, cardiovascular events and mortality. The subclinical Cushing's syndrome is not rare, being estimated to be between 0.2-2 % in the adult population. Despite the huge number of studies that have been published in the recent years, several issues remain controversial for the subclinical Cushing's syndrome screening, diagnosis and treatment. The Altogether to Beat Cushing's syndrome Group was founded in 2012 for bringing together the leading Italian experts in the hypercortisolism-related diseases. This document represents the Altogether to Beat Cushing's syndrome viewpoint regarding the following controversial issues on Subclinical Cushing's syndrome (SCS): (1) Who has to be screened for subclinical Cushing's syndrome? (2) How to screen the populations at risk? (3) How to diagnose subclinical Cushing's syndrome in patients with an adrenal incidentaloma? (4) Which consequence of subclinical Cushing's syndrome has to be searched for? (5) How to address the therapy of choice in AI patients with subclinical Cushing's syndrome? (6) How to follow-up adrenal incidentaloma patients with subclinical Cushing's syndrome surgically or conservatively treated? Notwithstanding the fact that most studies that faced these points may have several biases (e.g., retrospective design, small sample size, different criteria for the subclinical Cushing's syndrome diagnosis), we believe that the literature evidence is sufficient to affirm that the subclinical Cushing's syndrome condition is not harmless and that the currently available diagnostic tools are reliable for identifying the majority of individuals with subclinical Cushing's syndrome.

Differences in Cardiovascular Disease Risk between Nondiabetic Adults with Mental Retardation with and without Down Syndrome.

ERIC Educational Resources Information Center

Draheim, Christopher C.; McCubbin, Jeffrey A.; Williams, Daniel P.

2002-01-01

A study compared components of insulin resistance syndrome between 75 adults with Down syndrome and 70 with mental retardation. Women with Down syndrome had lower fasting plasma glucose and lower systolic blood pressure than comparison women. Men with Down syndrome had lower systolic and diastolic blood pressure than comparison men. (Contains…

Otitis Media in Young Children with Disabilities--Practical Strategies. FPG Snapshot #16

ERIC Educational Resources Information Center

FPG Child Development Institute, University of North Carolina, 2004

2004-01-01

Studies have shown that some children are at higher risk for otitis media. Those at risk may include children with some developmental disorders such as Down syndrome, Williams syndrome, Apert syndrome, fragile X syndrome, Turner syndrome, cleft palate, and autism; as well as all children attending childcare. It has been hypothesized that the link…

Behavioral Phenotype of Fragile X Syndrome in Adolescence and Adulthood

ERIC Educational Resources Information Center

Smith, Leann E.; Barker, Erin T.; Seltzer, Marsha Mailick; Abbeduto, Leonard; Greenberg, Jan S.

2012-01-01

The present study explored the behavioral profile of individuals with fragile X syndrome during adolescence and adulthood. Individuals with both fragile X syndrome and autism (n = 30) were compared with (a) individuals diagnosed with fragile X syndrome (but not autism; n = 106) and (b) individuals diagnosed with autism (but not fragile X syndrome;…

What Health Issues or Conditions Are Specific to Women Only?

MedlinePlus

... Research Information Find a Study Resources and Publications Turner Syndrome Condition Information NICHD Research Information Find a Study ... disorders and conditions that affect only women include Turner syndrome , Rett syndrome , and ovarian and cervical cancers. Issues ...

[Association Budd Chiari syndrome, antiphospholipid syndrome and Grave's disease].

PubMed

Mouelhi, Leila; Chaieb, Mouna; Debbeche, Radhouane; Salem, Mohamed; Sfar, Imene; Trabelsi, Sinda; Gorgi, Yosr; Najjar, Taoufik

2009-02-01

Antiphospholipid syndrome is revealed by Budd Chiari syndrome in 5% of the cases. Antiphospholipid syndrome is characterized by venous or arterial thrombosis, foetal loss and positivity of antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein I. Anticardiolipin antibodies was reported in auto-immune thyroid disorders, particularly in Grave's disease. Antiphospholipid syndrome associated to Grave's disease was reported in only three cases. To describe a case report of association of Grave's disease and antiphospholipid syndrome. We report the first case of Grave's disease associated with antiphospholipid syndrome, revealed by Budd Chiari syndrome. Our observation is particular by the fact that it is about a patient presenting a Grave's disease associated with antiphospholipid syndrome revealed by Budd Chiari syndrome. This triple association has never been reported in literature. Although association between antiphospholipid syndrome and Grave's disease was previously described, further studies evaluating the coexistence of these two affections in the same patient would be useful.

High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome.

PubMed

Worm, Signe W; Friis-Møller, Nina; Bruyand, Mathias; D'Arminio Monforte, Antonella; Rickenbach, Martin; Reiss, Peter; El-Sadr, Wafaa; Phillips, Andrew; Lundgren, Jens; Sabin, Caroline

2010-01-28

This study describes the characteristics of the metabolic syndrome in HIV-positive patients in the Data Collection on Adverse Events of Anti-HIV Drugs study and discusses the impact of different methodological approaches on estimates of the prevalence of metabolic syndrome over time. We described the prevalence of the metabolic syndrome in patients under follow-up at the end of six calendar periods from 2000 to 2007. The definition that was used for the metabolic syndrome was modified to take account of the use of lipid-lowering and antihypertensive medication, measurement variability and missing values, and assessed the impact of these modifications on the estimated prevalence. For all definitions considered, there was an increasing prevalence of the metabolic syndrome over time, although the prevalence estimates themselves varied widely. Using our primary definition, we found an increase in prevalence from 19.4% in 2000/2001 to 41.6% in 2006/2007. Modification of the definition to incorporate antihypertensive and lipid-lowering medication had relatively little impact on the prevalence estimates, as did modification to allow for missing data. In contrast, modification to allow the metabolic syndrome to be reversible and to allow for measurement variability lowered prevalence estimates substantially. The prevalence of the metabolic syndrome in cohort studies is largely based on the use of nonstandardized measurements as they are captured in daily clinical care. As a result, bias is easily introduced, particularly when measurements are both highly variable and may be missing. We suggest that the prevalence of the metabolic syndrome in cohort studies should be based on two consecutive measurements of the laboratory components in the syndrome definition.

Prevalence and risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers: a study on 1311 subjects.

PubMed

Hein, Matthieu; Lanquart, Jean-Pol; Loas, Gwénolé; Hubain, Philippe; Linkowski, Paul

2017-07-06

Several studies have investigated the prevalence and risk factors of insomnia in subjects with obstructive sleep apnea syndrome. However, few studies have investigated the prevalence and risk factors for obstructive sleep apnea syndrome in insomnia sufferers. Thus, the aim of this study was to examine the prevalence and risk factors of moderate to severe obstructive sleep apnea syndrome in a large sample of insomnia sufferers. Data from 1311 insomnia sufferers who were recruited from the research database of the sleep laboratory of the Erasme Hospital were analysed. An apnea-hypopnea index of ≥15 events per hour was used as the cut-off score for moderate to severe obstructive sleep apnea syndrome. Logistic regression analyses were conducted to examine clinical and demographic risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers. The prevalence of moderate to severe obstructive sleep apnea syndrome in our sample of insomnia sufferers was 13.88%. Multivariate logistic regression analysis revealed that male gender, snoring, excessive daytime sleepiness, lower maintenance insomnia complaint, presence of metabolic syndrome, age ≥ 50 & <65 years, age ≥ 65 years, BMI ≥ 25 & <30 kg/m 2 , BMI >30 kg/m 2 , and CRP >7 mg/L were significant risk factors of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers. Moderate to severe obstructive sleep apnea syndrome is a common pathology in insomnia sufferers. The identification of these different risk factors advances a new perspective for more effective screening of moderate to severe obstructive sleep apnea syndrome in insomnia sufferers.

Association between pancreatic fat and incidence of metabolic syndrome: a 5-year Japanese cohort study.

PubMed

Yamazaki, Hajime; Tauchi, Shinichi; Kimachi, Miho; Dohke, Mitsuru; Hanawa, Nagisa; Kodama, Yoshihisa; Katanuma, Akio; Yamamoto, Yosuke; Fukuma, Shingo; Fukuhara, Shunichi

2018-04-26

Previous cross-sectional studies showed that pancreatic fat was associated with metabolic syndrome. However, no longitudinal study has evaluated whether people with high pancreatic fat are likely to develop future metabolic syndrome. This study investigated the association between baseline pancreatic fat and metabolic syndrome incidence. In 2008-2009, 320 participants without metabolic syndrome underwent health checks, which included unenhanced computed tomography, and were followed up annually for 4-5 years. Baseline pancreatic fat amounts were evaluated using a histologically validated method that measured differences between pancreas and spleen attenuations on computed tomography. The participants were divided into low (reference), intermediate, and high pancreatic fat groups based on pancreas and spleen attenuation tertiles. Metabolic syndrome incidence was evaluated annually over a median follow-up period of 4.99 (interquartile range, 4.88-5.05) years, in accordance with the 2009 harmonized criteria. Risk ratios (RRs) for the association between baseline pancreatic fat amounts and metabolic syndrome incidence were estimated using Poisson regression models adjusted for age, sex, body mass index, liver fat, pre-metabolic syndrome, cigarette use, alcohol use, and physical activity. Metabolic syndrome incidence was 30.6% (98/320). Pancreatic fat was associated with an increased incidence of metabolic syndrome, based on a univariate analysis (RRs [95% confidence interval], 3.14 [1.74-5.67] and 3.96 [2.23-7.03] in the intermediate and high pancreatic fat groups, respectively). The association remained statistically significant in the multivariate analysis (RR [95% confidence interval], 2.04 [1.14-3.64] and 2.30 [1.28-4.14] for the same groups, respectively). Pancreatic fat predicts the future risk of metabolic syndrome. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

VARIABILITY IN ASSOCIATIONS OF PHOSPHATIDYCHOLINE MOLECULAR SPECIES WITH METABOLIC SYNDROME IN MEXICAN-AMERICAN FAMILIES

PubMed Central

Kulkarni, Hemant; Meikle, Peter J.; Mamtani, Manju; Weir, Jacquelyn M.; Barlow, Christopher K.; Jowett, Jeremy B.; Bellis, Claire; Dyer, Thomas D.; Johnson, Matthew P.; Rainwater, David L.; Almasy, Laura; Mahaney, Michael C.; Comuzzie, Anthony G.; Blangero, John; Curran, Joanne E.

2013-01-01

Plasma lipidomic studies using high performance liquid chromatography and mass spectroscopy offer detailed insights into metabolic processes. Taking the example of the most abundant plasma lipid class (phosphatidylcholines) we used the rich phenotypic and lipidomic data from the ongoing San Antonio Family Heart Study of large extended Mexican American families to assess the variability of association of the plasma phosphatidylcholine species with metabolic syndrome. Using robust statistical analytical methods, our study made two important observations. First, there was a wide variability in the association of phosphatidylcholine species with risk measures of metabolic syndrome. Phosphatidylcholine 40:7 was associated with a low risk while phosphatidylcholines 32:1 and 38:3 were associated with a high risk of metabolic syndrome. Second, all the odd chain phosphatidylcholines were associated with a reduced risk of metabolic syndrome implying that phosphatidylcholines derived from dairy products might be beneficial against metabolic syndrome. Our results demonstrate the value of lipid species-specific information provided by the upcoming array of lipidomic studies and open potential avenues for prevention and control of metabolic syndrome in high prevalence settings. PMID:23494580

Eligibility for clinical trials in primary Sjögren’s syndrome: lessons from the UK Primary Sjögren’s Syndrome Registry

PubMed Central

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T.; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J.

2016-01-01

Abstract Objective: To identify numbers of participants in the UK Primary Sjögren’s Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. Methods: We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. Results: In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren’s Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren’s syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren’s Syndrome study (Tocilizumab), 46.3% for the Tolerance and Efficacy of Rituximab in Sjögren’s Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren’s Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. Conclusion: The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. PMID:26510429

New insights on diabetes in Turner syndrome: results from an observational study in adulthood.

PubMed

Ibarra-Gasparini, Daniela; Altieri, Paola; Scarano, Emanuela; Perri, Annamaria; Morselli-Labate, Antonio M; Pagotto, Uberto; Mazzanti, Laura; Pasquali, Renato; Gambineri, Alessandra

2018-03-01

To explore the characteristics of diabetes mellitus in adults with Turner syndrome. Observational study consisting of a prospective phase after the access of adults with Turner syndrome to the Endocrinology Unit (median period of follow-up 15.6, interquartile range: 12.0-24.5 months) and a retrospective collection of data from the diagnosis of Turner syndrome until the time of access to the Endocrinology Unit. A total of 113 Italian Turner syndrome patients were included in the study. During the prospective phase of the study, each patient underwent physical examination, fasting blood sampling, and an oral glucose tolerance test on a yearly basis. Oral glucose tolerance test was used to perform the diagnosis of diabetes mellitus. Before access to the Endocrinology Unit, diabetes mellitus was diagnosed in two Turner syndrome patients. Another five cases of diabetes mellitus were diagnosed at the first access to the Endocrinology Unit, whereas seven new cases of diabetes mellitus were diagnosed during the prospective phase of the study. At the diagnosis of diabetes mellitus, only one patient had fasting glucose above 126 mg/dL, and only two had an HbA1c value >6.5% (48 mmol/mol). When compared to normo-glucose tolerant patients, the diabetic patients had a significantly lower insulin-to-glucose ratio at 30 and 60 min of the oral glucose tolerance test. In the regression analyses, only age was associated with the development of diabetes mellitus. This study confirms that diabetes mellitus is frequent in Turner syndrome and suggests that it is specific to the syndrome. In addition, this study demonstrates that oral glucose tolerance test is a more sensitive test than HbA1c for the diagnosis of diabetes mellitus in Turner syndrome.

Eligibility for clinical trials in primary Sjögren's syndrome: lessons from the UK Primary Sjögren's Syndrome Registry.

PubMed

Oni, Clare; Mitchell, Sheryl; James, Katherine; Ng, Wan-Fai; Griffiths, Bridget; Hindmarsh, Victoria; Price, Elizabeth; Pease, Colin T; Emery, Paul; Lanyon, Peter; Jones, Adrian; Bombardieri, Michele; Sutcliffe, Nurhan; Pitzalis, Costantino; Hunter, John; Gupta, Monica; McLaren, John; Cooper, Annie; Regan, Marian; Giles, Ian; Isenberg, David; Saravanan, Vadivelu; Coady, David; Dasgupta, Bhaskar; McHugh, Neil; Young-Min, Steven; Moots, Robert; Gendi, Nagui; Akil, Mohammed; Barone, Francesca; Fisher, Ben; Rauz, Saaeha; Richards, Andrea; Bowman, Simon J

2016-03-01

To identify numbers of participants in the UK Primary Sjögren's Syndrome Registry (UKPSSR) who would fulfil eligibility criteria for previous/current or potential clinical trials in primary SS (pSS) in order to optimize recruitment. We did a retrospective analysis of UKPSSR cohort data of 688 participants who had pSS with evaluable data. In relation to previous/current trials, 75.2% fulfilled eligibility for the Belimumab in Subjects with Primary Sjögren's Syndrome study (Belimumab), 41.4% fulfilled eligibility for the Trial of Remicade in primary Sjögren's syndrome study (Infliximab), 35.4% for the Efficacy of Tocilizumab in Primary Sjögren's Syndrome study (Tocilizumab), 31.6% for the Tolerance and Efficacy of Rituximab in Sjögren's Disease study (Rituximab), 26.9% for the Trial of anti-B-cell therapy in pSS study (Rituximab) and 26.6% for the Efficacy and Safety of Abatacept in Patients With Primary Sjögren's Syndrome study (Abatacept). If recent measures of outcome, such as the EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score ⩾5 (measure of patient symptoms) and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score ⩾5 (measure of systemic disease activity) are incorporated into a study design, with requirements for an unstimulated salivary flow >0 and anti-Ro positivity, then the pool of eligible participants is reduced to 14.3%. The UKPSSR identified a number of options for trial design, including selection on ESSDAI ⩾5, ESSPRI ⩾5 and serological and other parameters. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Brief Report: Syndromes in Autistic Children in a Finnish Birth Cohort.

PubMed

Timonen-Soivio, Laura; Vanhala, Raija; Malm, Heli; Hinkka-Yli-Salomäki, Susanna; Gissler, Mika; Brown, Alan; Sourander, Andre

2016-08-01

We studied the association between specific congenital syndromes and autism spectrum disorders (ASD) in the large Finnish Register material. Our data include all children diagnosed with ASD (n = 4441) according to Finnish Hospital Discharge Register in 1987-2000. Four controls per each case were matched to sex, birthplace, date of birth (±30 days) and residence in Finland (n = 17,695). The prevalence of specific congenital syndromes in the Finnish Register of Congenital Malformations was evaluated among the ASD group and the controls by sex. The results of this study suggest that there is an association between several etiologically different syndromes and ASD when compared to controls without ASD. Statistically significant associations were observed with 47,XYY, Sotos syndrome, neurofibromatosis I, and syndrome not otherwise specified. Syndromes were more common among males with ASD compared to controls. These results support the previous studies of etiological heterogeneity of ASD and have importance in clinical examination, management and rehabilitation.

Genetic testing for retinal dystrophies and dysfunctions: benefits, dilemmas and solutions.

PubMed

Koenekoop, Robert K; Lopez, Irma; den Hollander, Anneke I; Allikmets, Rando; Cremers, Frans P M

2007-07-01

Human retinal dystrophies have unparalleled genetic and clinical diversity and are currently linked to more than 185 genetic loci. Genotyping is a crucial exercise, as human gene-specific clinical trials to study photoreceptor rescue are on their way. Testing confirms the diagnosis at the molecular level and allows for a more precise prognosis of the possible future clinical evolution. As treatments are gene-specific and the 'window of opportunity' is time-sensitive; accurate, rapid and cost-effective genetic testing will play an ever-increasing crucial role. The gold standard is sequencing but is fraught with excessive costs, time, manpower issues and finding non-pathogenic variants. Therefore, no centre offers testing of all currently 132 known genes. Several new micro-array technologies have emerged recently, that offer rapid, cost-effective and accurate genotyping. The new disease chips from Asper Ophthalmics (for Stargardt dystrophy, Leber congenital amaurosis [LCA], Usher syndromes and retinitis pigmentosa) offer an excellent first pass opportunity. All known mutations are placed on the chip and in 4 h a patient's DNA is screened. Identification rates (identifying at least one disease-associated mutation) are currently approximately 70% (Stargardt), approximately 60-70% (LCA) and approximately 45% (Usher syndrome subtype 1). This may be combined with genotype-phenotype correlations that suggest the causal gene from the clinical appearance (e.g. preserved para-arteriolar retinal pigment epithelium suggests the involvement of the CRB1 gene in LCA). As approximately 50% of the retinal dystrophy genes still await discovery, these technologies will improve dramatically as additional novel mutations are added. Genetic testing will then become standard practice to complement the ophthalmic evaluation.

Defibrotide Stimulates Angiogenesis and Protects Endothelial Cells from Calcineurin Inhibitor-Induced Apoptosis via Upregulation of AKT/Bcl-xL.

PubMed

Wang, Xiangmin; Pan, Bin; Hashimoto, Yuko; Ohkawara, Hiroshi; Xu, Kailin; Zeng, Lingyu; Ikezoe, Takayuki

2018-01-01

Sinusoidal obstruction syndrome is a life-threatening complication that can occur after haematopoietic stem cell transplantation. Defibrotide (DF) has been approved for the treatment of individuals with severe sinusoidal obstruction syndrome following haematopoietic stem cell transplantation in the European Union and the United States. However, the precise mechanisms by which DF protects endothelial cells remain to be elucidated. In this study, we found that DF stimulated angiogenesis in vitro and in vivo as assessed by vascular tube formation, scratch-wound repair and Matrigel plug assays. These effects were associated with an activation of pro-survival signalling pathways, including AKT (protein kinase B), ERK (extracellular signal-regulated kinases) and p38. More importantly, DF alleviated calcineurin inhibitor-induced growth inhibition and apoptosis of human umbilical vein endothelial cells and human hepatic sinusoidal endothelial cells in parallel with upregulation of anti-apoptotic protein B-cell lymphoma-extra-large (Bcl-xL), which was mediated by AKT (protein kinase B). Notably, these effects were abrogated when Bcl-xL was depleted by small interfering RNA (ribonucleic acid). In addition, DF counteracted calcineurin inhibitor-induced activation of nuclear factor-κB and Janus kinase 2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signalling and production of cytokines in vascular endothelial cell-derived EA.hy926 cells. Taken together, DF has pro-angiogenic, anti-apoptotic and anti-inflammatory effects on endothelial cells. DF is a potentially useful agent to prevent the development of, and treat individuals with, endothelial cell injury-related complications after haematopoietic stem cell transplantation. Schattauer GmbH Stuttgart.

Iron overload promotes mitochondrial fragmentation in mesenchymal stromal cells from myelodysplastic syndrome patients through activation of the AMPK/MFF/Drp1 pathway.

PubMed

Zheng, Qingqing; Zhao, Youshan; Guo, Juan; Zhao, Sida; Fei, Chengming; Xiao, Chao; Wu, Dong; Wu, Lingyun; Li, Xiao; Chang, Chunkang

2018-05-03

Iron overload (IO) has been reported to contribute to mesenchymal stromal cell (MSC) damage, but the precise mechanism has yet to be clearly elucidated. In this study, we found that IO increased cell apoptosis and lowered cell viability in MSCs, accompanied by extensive mitochondrial fragmentation and autophagy enhancement. All these effects were reactive oxygen species (ROS) dependent. In MSCs with IO, the ATP concentrations were significantly reduced due to high ROS levels and low electron respiratory chain complex (ETC) II/III activity. Reduced ATP phosphorylated AMP-activated protein kinase (AMPK). Activation of AMPK kinase complexes triggered mitochondrial fission. Moreover, gene knockout of AMPK via CRISPR/Cas9 reduced cell apoptosis, enhanced cell viability and attenuated mitochondrial fragmentation and autophagy caused by IO in MSCs. Further, AMPK-induced mitochondrial fragmentation of MSCs with IO was mediated via phosphorylation of mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for the GTPase dynamin-related protein 1 (Drp1). Gene knockdown of MFF reversed AMPK-induced mitochondrial fragmentation in MSCs with IO. In addition, MSCs from IO patients with myelodysplastic syndrome (MDS) showed increased cell apoptosis, decreased cell viability, higher ROS levels, lower ATP concentrations and increased mitochondrial fragmentation compared with MSCs from non-IO patients. In addition, iron chelation or antioxidant weakened the activity of the AMPK/MFF/Drp1 pathway in MDS-MSCs with IO from several patients, accompanied by attenuation of mitochondrial fragmentation and autophagy. Taken together, the AMPK/MFF/Drp1 pathway has an important role in the damage to MDS-MSCs caused by IO.

Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

PubMed Central

Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.

2016-01-01

Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

WASp family verprolin-homologous protein-2 (WAVE2) and Wiskott-Aldrich syndrome protein (WASp) engage in distinct downstream signaling interactions at the T cell antigen receptor site.

PubMed

Pauker, Maor H; Reicher, Barak; Joseph, Noah; Wortzel, Inbal; Jakubowicz, Shlomi; Noy, Elad; Perl, Orly; Barda-Saad, Mira

2014-12-12

T cell antigen receptor (TCR) engagement has been shown to activate pathways leading to actin cytoskeletal polymerization and reorganization, which are essential for lymphocyte activation and function. Several actin regulatory proteins were implicated in regulating the actin machinery, such as members of the Wiskott-Aldrich syndrome protein (WASp) family. These include WASp and the WASp family verprolin-homologous protein-2 (WAVE2). Although WASp and WAVE2 share several structural features, the precise regulatory mechanisms and potential redundancy between them have not been fully characterized. Specifically, unlike WASp, the dynamic molecular interactions that regulate WAVE2 recruitment to the cell membrane and specifically to the TCR signaling complex are largely unknown. Here, we identify the molecular mechanism that controls the recruitment of WAVE2 in comparison with WASp. Using fluorescence resonance energy transfer (FRET) and novel triple-color FRET (3FRET) technology, we demonstrate how WAVE2 signaling complexes are dynamically regulated during lymphocyte activation in vivo. We show that, similar to WASp, WAVE2 recruitment to the TCR site depends on protein-tyrosine kinase, ZAP-70, and the adaptors LAT, SLP-76, and Nck. However, in contrast to WASp, WAVE2 leaves this signaling complex and migrates peripherally together with vinculin to the membrane leading edge. Our experiments demonstrate that WASp and WAVE2 differ in their dynamics and their associated proteins. Thus, this study reveals the differential mechanisms regulating the function of these cytoskeletal proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

WASp Family Verprolin-homologous Protein-2 (WAVE2) and Wiskott-Aldrich Syndrome Protein (WASp) Engage in Distinct Downstream Signaling Interactions at the T Cell Antigen Receptor Site*

PubMed Central

Pauker, Maor H.; Reicher, Barak; Joseph, Noah; Wortzel, Inbal; Jakubowicz, Shlomi; Noy, Elad; Perl, Orly; Barda-Saad, Mira

2014-01-01

T cell antigen receptor (TCR) engagement has been shown to activate pathways leading to actin cytoskeletal polymerization and reorganization, which are essential for lymphocyte activation and function. Several actin regulatory proteins were implicated in regulating the actin machinery, such as members of the Wiskott-Aldrich syndrome protein (WASp) family. These include WASp and the WASp family verprolin-homologous protein-2 (WAVE2). Although WASp and WAVE2 share several structural features, the precise regulatory mechanisms and potential redundancy between them have not been fully characterized. Specifically, unlike WASp, the dynamic molecular interactions that regulate WAVE2 recruitment to the cell membrane and specifically to the TCR signaling complex are largely unknown. Here, we identify the molecular mechanism that controls the recruitment of WAVE2 in comparison with WASp. Using fluorescence resonance energy transfer (FRET) and novel triple-color FRET (3FRET) technology, we demonstrate how WAVE2 signaling complexes are dynamically regulated during lymphocyte activation in vivo. We show that, similar to WASp, WAVE2 recruitment to the TCR site depends on protein-tyrosine kinase, ZAP-70, and the adaptors LAT, SLP-76, and Nck. However, in contrast to WASp, WAVE2 leaves this signaling complex and migrates peripherally together with vinculin to the membrane leading edge. Our experiments demonstrate that WASp and WAVE2 differ in their dynamics and their associated proteins. Thus, this study reveals the differential mechanisms regulating the function of these cytoskeletal proteins. PMID:25342748

Carbohydrate restriction improves the features of Metabolic Syndrome. Metabolic Syndrome may be defined by the response to carbohydrate restriction.

PubMed

Volek, Jeff S; Feinman, Richard D

2005-11-16

Metabolic Syndrome (MetS) represents a constellation of markers that indicates a predisposition to diabetes, cardiovascular disease and other pathologic states. The definition and treatment are a matter of current debate and there is not general agreement on a precise definition or, to some extent, whether the designation provides more information than the individual components. We consider here five indicators that are central to most definitions and we provide evidence from the literature that these are precisely the symptoms that respond to reduction in dietary carbohydrate (CHO). Carbohydrate restriction is one of several strategies for reducing body mass but even in the absence of weight loss or in comparison with low fat alternatives, CHO restriction is effective at ameliorating high fasting glucose and insulin, high plasma triglycerides (TAG), low HDL and high blood pressure. In addition, low fat, high CHO diets have long been known to raise TAG, lower HDL and, in the absence of weight loss, may worsen glycemic control. Thus, whereas there are numerous strategies for weight loss, a patient with high BMI and high TAG is likely to benefit most from a regimen that reduces CHO intake. Reviewing the literature, benefits of CHO restriction are seen in normal or overweight individuals, in normal patients who meet the criteria for MetS or in patients with frank diabetes. Moreover, in low fat studies that ameliorate LDL and total cholesterol, controls may do better on the symptoms of MetS. On this basis, we feel that MetS is a meaningful, useful phenomenon and may, in fact, be operationally defined as the set of markers that responds to CHO restriction. Insofar as this is an accurate characterization it is likely the result of the effect of dietary CHO on insulin metabolism. Glucose is the major insulin secretagogue and insulin resistance has been tied to the hyperinsulinemic state or the effect of such a state on lipid metabolism. The conclusion is probably not surprising but has not been explicitly stated before. The known effects of CHO-induced hypertriglyceridemia, the HDL-lowering effect of low fat, high CHO interventions and the obvious improvement in glucose and insulin from CHO restriction should have made this evident. In addition, recent studies suggest that a subset of MetS, the ratio of TAG/HDL, is a good marker for insulin resistance and risk of CVD, and this indicator is reliably reduced by CHO restriction and exacerbated by high CHO intake. Inability to make this connection in the past has probably been due to the fact that individual responses have been studied in isolation as well as to the emphasis of traditional therapeutic approaches on low fat rather than low CHO. We emphasize that MetS is not a disease but a collection of markers. Individual physicians must decide whether high LDL, or other risk factors are more important than the features of MetS in any individual case but if MetS is to be considered it should be recognized that reducing CHO will bring improvement. Response of symptoms to CHO restriction might thus provide a new experimental criterion for MetS in the face of on-going controversy about a useful definition. As a guide to future research, the idea that control of insulin metabolism by CHO intake is, to a first approximation, the underlying mechanism in MetS is a testable hypothesis.

Targeted pharmacological treatment of autism spectrum disorders: fragile X and Rett syndromes

PubMed Central

Wang, Hansen; Pati, Sandipan; Pozzo-Miller, Lucas; Doering, Laurie C.

2015-01-01

Autism spectrum disorders (ASDs) are genetically and clinically heterogeneous and lack effective medications to treat their core symptoms. Studies of syndromic ASDs caused by single gene mutations have provided insights into the pathophysiology of autism. Fragile X and Rett syndromes belong to the syndromic ASDs in which preclinical studies have identified rational targets for drug therapies focused on correcting underlying neural dysfunction. These preclinical discoveries are increasingly translating into exciting human clinical trials. Since there are significant molecular and neurobiological overlaps among ASDs, targeted treatments developed for fragile X and Rett syndromes may be helpful for autism of different etiologies. Here, we review the targeted pharmacological treatment of fragile X and Rett syndromes and discuss related issues in both preclinical studies and clinical trials of potential therapies for the diseases. PMID:25767435

A Review of Differences in Clinical Characteristics between Tardive Syndrome Induced or Improved by Aripiprazole Treatment.

PubMed

Chen, Yen-Wen; Tseng, Ping-Tao

2016-09-15

Tardive syndrome is a troublesome complication secondary to the long-term usage of antipsychotic medication. At present, there is a lack of effective treatment for tardive syndrome. Aripiprazole has been used in the treatment of tardive syndrome, with some reports of a good response. However, other reports have suggested that tardive syndrome can actually be induced by aripiprazole. The aim of current study was to investigate whether aripiprazole is beneficial or harmful for the treatment of tardive syndrome in specific patients. We performed a thorough literature search via PubMed. We included all of the studies discussing the relationship between tardive syndrome and aripiprazole, either with regards to "inducing" or "improving" the disease. None of the included studies were well-designed clinical trials, and all were case reports or case series. A total of 26 articles were included in which aripiprazole induced tardive syndrome, and another 24 in which tardive syndrome was improved by aripiprazole treatment. In the "improved" group, there were significantly more cases of schizophrenia than in the "induced" group (p=0.002). However, there were significantly more cases with other miscellaneous diagnoses in the "induced" group than in the "improved" group (p=0.003). In addition, the cases in the "induced" group had a significantly longer duration of aripiprazole usage than those in the "improved" group (p=0.001). Current study is important for clinicians to pay attention to the risk of tardive syndrome when prescribing aripiprazole in patients with a diagnosis other than a psychiatric illness or in the long-term administration of aripiprazole.